bluuebunny/crossref_metadata_2025 huggingface dataset:
Leydig cell resistance to the cytotoxic effect of ethylene dimethanesulphonate in the adult rat testis
Authors: Morris I. D.
Published: December 2008

Weekly doses of the Leydig cell cytotoxic ethylene dimethanesulphonate (EDS) were administered to adult male rats in an attempt to study the endocrine activity of the testis in the absence of Leydig cells. One week after the first dose serum testosterone and LH concentrations and seminal vesicle weights were close to levels in castrated rats and testicular human chorionic gonadotrophin (hCG) binding was severely depressed. These changes were maintained for a further week but subsequently began to return to, but did not achieve, control levels. After six weekly doses seminal vesicle weight and serum testosterone concentrations were significantly higher than in the castrated rats. Serum LH concentrations were declining towards control values at 4 weeks but had risen again at 6 weeks. Serum FSH concentrations were raised to about 50% of the value in castrated rats throughout the period studied. Testis weight and hCG binding, which initially fell, were partially restored at 6 weeks and spermatogenesis was recovering. The data show that responses of the testis to multiple doses of EDS are similar to those after a single dose. This apparent resistance indicates that the regenerating Leydig cells are functionally different from the mature Leydig cell. The similarities between the maturing Leydig cell seen after EDS destruction and those in the immature rat suggest that EDS will provide a valuable model for the investigation of Leydig cell physiology.

J. Endocr. (1985) 105, 311–316
Effect of hypophysectomy on cyclic 3′,5′-nucleotide-metabolizing enzymes in the rat thyroid gland
Authors: Nagasaka A. , Hidaka H. , Itoh H. , Nakagawa H. , Kataoka K. , Yamaguchi A. , Iwase K. , Nakai A. , Ohyama T. , Aono T. , Miyakawa S. , Kawase K. , Miura K.
Published: December 2008

Adenylate cyclase and cyclic AMP phosphodiesterase activities in the thyroid gland were significantly reduced after hypophysectomy, followed by a gradual restoration of the enzyme activities to the levels seen in sham-operated rats whereas a slight and persistent reduction was evident in guanylate cyclase and cyclic GMP phosphodiesterase activities in the same tissue. These changes in enzyme activities were restored by TSH administration but not by ACTH. The recovery of activity produced by TSH administration was inhibited by cycloheximide. Hypophysectomy, or TSH and cycloheximide administration, did not produce any significant changes in the concentrations of calmodulin, suggesting that the alteration of these enzyme activities is not induced by a decrease in the concentration of calmodulin. Since forskolin activation of adenylate cyclase did not restore the reduced activity in the hypophysectomized rat thyroid to the level found in the sham-operated control rat thyroid, we conclude that there is a reduction of the amount of enzyme after hypophysectomy rather than a change of the active site on adenylate cyclase. The spontaneous restoration of adenylate cyclase and cyclic AMP phosphodiesterase activities after hypophysectomy implies that cyclic AMP-metabolizing enzymes are responsive to an autoregulatory mechanism in thyroid follicular cells.

J. Endocr. (1985) 105, 363–369
Antagonism by growth hormone of insulin action in fetal sheep
Authors: Parkes M. J. , Bassett J. M.
Published: December 2008

Insulin, glucose, lactate and alpha-amino acid nitrogen concentrations were measured in the plasma of ewes and their hypophysectomized fetal lambs during intravenous infusions of GH, prolactin or saline into the fetus in utero. Prolactin and saline had no effect on mother or fetus. Infusion of GH at 1·2 mg/kg per day for 2 days or at 0·4 mg/kg per day for 4 days caused a sustained twofold increase in the level of insulin and a smaller, but sustained, increase in the level of glucose in fetal plasma. We suggest that GH antagonizes the action of insulin in the fetus. Glucose supplies to the fetal brain and placenta may be protected by such antagonism of insulin use during glucose shortage.

J. Endocr. (1985) 105, 379–382
CHARACTERISATION BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY OF CIRCULATING GROWTH HORMONE RELEASING FACTORS IN A HUMAN PLASMA
Authors: Penny E.S. , Patience R.L. , Sopwith A.M. , Wass J.A.H. , Besser G.M. , Rees L.H.
Published: December 2008

Three forms of circulating immunoreactive human growth hormone-releasing factor (ir-hGRF) have been identified from a patient whose acromegaly was associated with a disseminated carcinoid tumour. This is the first known report of the molecular forms of ir-hGRF in human plasma. High performance liquid chromatography (HPLC) on a C3, wide pore reversed-phase column and gel filtration chromatography were used in conjunction with a sensitive radioimmunoassay (RIA). The greatly elevated concentration of the ir-hGRF in plasma from this patient was 25,000 ng/l (normal range <60 ng/l). Gel filtration (G50) chromatography of the plasma revealed a single peak which coeluted with synthetic hGRF-40. However, reversed-phase HPLC of Vycorextracted plasma resolved the ir-hGRF into three components, which coeluted with synthetic hGRF-40 (69%), hGRF-44 (22%) and hGRF-37 (9%). At present it is not clear if the three forms are natural variants or whether either or both hGRF-40 and hGRF-37 are cleavage products of hGRF-44.
Effect of restriction of placental growth on the concentrations of insulin, glucose and placental lactogen in the plasma of sheep
Authors: Falconer J. , Owens J. A. , Allotta E. , Robinson J. S.
Published: December 2008

The effect of restricting placental growth on maternal glucose, insulin and placental lactogen was investigated in 16 ewes carrying singleton lambs. Uterine caruncles were removed from seven ewes (caruncle ewes) before pregnancy, resulting in reduced placental size and retarded intra-uterine fetal growth. The concentration of insulin in maternal plasma was similar in both control and caruncle ewes. The concentration of glucose was significantly higher in the caruncle than in the control ewes (3·26 ± 0·15 (s.e.m.) mmol/l, number of observations (n) = 9, vs 2·75 ± 0·1, n = 9, P<0·02, and 3·27 ±0·16, n = 7, vs 2·46± 0·11, n = 12, P<0·001, for the carotid artery and utero-ovarian vein respectively). The concentration of ovine placental lactogen (oPL) in the utero-ovarian vein was reduced in the caruncle compared with the control ewes (283± 65 μg/l, n = and 705±106 μg/l, n = 18, P<0·02, respectively). Restriction of placental growth by removal of endometrial caruncles similarly reduced the concentrations of oPL in maternal arterial plasma (231±54 μg/l, n = 9, and 621±96 μg/l, n = 18, P<0·002). Production of oPL by the placenta was also reduced by limiting placental growth to 30±11 μg/min, n = 8, compared with 133±43 μg/min, n = 15, P<0·05, for the controls. Production of oPL per gram of placenta in the caruncle group, although only 34% of the control value, was not reduced significantly. These observations are consistent with the hypothesis that oPL may be involved in the redirection of maternal glucose during pregnancy to maximize the amount available for the fetus.

J. Endocr. (1985) 106, 7–11
Precocious ovulation induced by human chorionic gonadotrophin in the immature female rat: comparison of follicle growth induced by treatment with human chorionic gonadotrophin and by electrical stimulation of the hypothalamus
Authors: Meijs-Roelofs H. M. A. , Kramer P. , Osman P.
Published: December 2008

Precocious first ovulation, preceded by an endogenous preovulatory LH surge, could be predictably induced in immature female rats by administering repeated injections of human chorionic gonadotrophin (hCG). Administration of a dose of 0·05–0·075 i.u. hCG, four times a day from day 28 to day 31 of age resulted in a highly constant ovulatory response: at 4·0±0·0 days after the start of treatment 7·7±0·3 (n = 15) ova were found. Use of a higher dose of hCG (0·1 i.u.) resulted in lower numbers of ova (5·6±0·4, n = 7; P<0·005) whereas use of a lower dose of hCG (0·025–0·038 i.u.) resulted in a less constant timing of the induced ovulation at 5·4±0·2 days after the start of treatment (n = 7; P<0·0005). In animals treated with the dose of 0·05–0·075 i.u. hCG, a positive correlation was found between body weight at the start of treatment and the number of ova released (r = 0·75, n = 25; P<0·001).

Ovarian follicle dynamics were studied on the various days of hCG treatment (dose 0·05–0·075 i.u.) and compared with the follicle changes that take place after electrical stimulation of the hypothalamus, performed on day 28, a treatment known to result in first ovulation 4–5 days later. In both groups a decrease in the number of the smallest and the middle-sized antral follicles as compared with their respective controls was seen, whereas numbers of follicles in the largest, 'ovulatable' size classes gradually increased. The pattern was more conspicuous in the hCG-treated group, presumably related to greater constancy in timing of the ovulatory response in this group.

The present data support the view that endogenous changes in LH secretion during late prepuberty (which have been found to take place) play a significant role in stimulating late-prepubertal follicle growth and the ensuing first ovulation.

J. Endocr. (1985) 106, 61–66
Induction of ovulation in vitro in the hen: dependency of the response to LH on age and rate of lay
Authors: Moudgal R. P. , Razdan M. N.
Published: December 2008

Two experiments were conducted on White Leghorn hens to investigate the effect of different concentrations of LH on the frequency of induction of ovulation in vitro of ovarian follicles collected 18–20 h before the expected time of ovulation from birds of three different ages (7, 18 and 30 months) or of the same age but laying short (three to four) or long (more than seven) sequences of eggs. The ability of LH to induce ovulation was directly related to the age of the donors of the follicles. Follicles derived from hens laying short sequences of eggs were less responsive to the ovulation-inducing effects of LH than were follicles from birds laying long sequences. These observations suggest that the sensitivity of ovarian follicles to the ovulation-inducing effects of LH declines with age and is greater in hens laying long sequences of eggs than those laying short sequences.

J. Endocr. (1985) 106, 67–69
Infantile ovariectomy potentiates the stimulatory effect of oestrogen/progesterone on LH secretion in the rat
Authors: Wilkinson M. , Bhanot R.
Published: December 2008

Ovariectomy of prepubertal rats (9 days of age) eliminates the ability of the opiate peptide FK 33-824 to inhibit LH secretion when tested 19 days later. We have investigated whether this removal of opiate inhibition would modify the LH/FSH response to stimulation with oestradiol benzoate/progesterone priming. Ovariectomy of rats during infancy (9 days after birth) amplifies the stimulatory effects of these steroids on LH/FSH secretion when tested 19 days later. This amplification was not seen in rats ovariectomized before (day 24) or after puberty (day 43) and tested 19 days later. The pituitary content of LH/FSH does not appear to contribute to this phenomenon, though increased responsiveness to injected gonadotrophin-releasing hormone (GnRH) is clearly involved; ovariectomy at day 9 is considerably more effective than ovariectomy at day 24 of life in enhancing the response to GnRH.

We conclude that infantile ovariectomy either removes, or prevents the development of, a hypothalamic inhibitory mechanism which normally modulates the responsiveness of the pituitary to stimulation with GnRH.

J. Endocr. (1985) 106, 133–139
Influence of neonatal hemicastration on in-vitro secretion of inhibin, gonadotrophins and testicular steroids in male rats
Authors: Ultee-van Gessel A. M. , Leemborg F. G. , de Jong F. H. , van der Molen H. J.
Published: December 2008

Pituitary secretion of FSH in male animals is regulated, at least partly, by a protein hormone, inhibin, which is produced by Sertoli cells in the testes. To establish at which age the role of testicular inhibin in the regulation of FSH secretion becomes apparent, groups of male rats were hemicastrated or sham-operated on day 1 of life and pituitary and testicular function were investigated in vitro at 21, 42 or 63 days of age.

Testis weights were increased in hemicastrated rats at all ages studied. Peripheral concentrations of gonadotrophins generally showed a good correlation with the concentrations of FSH and LH measured in the medium of hemipituitary glands which were incubated in vitro at 37 °C in the absence or presence of LH-releasing hormone. Peripheral testosterone concentrations in hemicastrated animals were not significantly different from those in sham-operated rats at all ages studied. Steroid production by Leydig cells in vitro was not significantly influenced by hemicastration. The secretion of inhibin by Sertoli cells from 21-day-old hemicastrated rats was decreased while Sertoli cells from 42- and 63-day-old hemicastrated animals secreted slightly but not significantly more inhibin than Sertoli cells from sham-operated rats.

It is concluded that although compensatory increases of testosterone and inhibin production at later ages make it difficult to draw conclusions about the relative importance of inhibin in the feedback regulation of FSH secretion at different ages, it is likely that inhibin plays a role in the feedback of FSH in immature, rather than in mature male rats.

J. Endocr. (1985) 106, 259–265
Hydrolysis of deoxycorticosterone-21-yl sulphate and dehydroepiandrosterone sulphate by microsomal preparations of human placentae: evidence for a common enzyme
Authors: Egyed J. , Oakey R. E.
Published: December 2008

The human placenta can hydrolyse both dehydroepiandrosterone-3β-yl sulphate (DHASO4−) and deoxycorticosterone-21-yl sulphate (DOCSO4−). There is some uncertainty as to whether the same or different enzymes are responsible for hydrolysis of these substrates. As a fresh approach to this problem we have compared the quantities of DHASO4− and DOCSO4− hydrolysed by microsomal preparations of placentae obtained from 14 normal pregnancies and from 14 pregnancies complicated by steroid sulphatase deficiency.

Under the conditions used, and standardizing the results to unit time and quantity of protein, 1380–8830 fmol DHASO4− were hydrolysed by 14 normal placentae whereas < 1000 fmol DHASO4− were hydrolysed by the other 14 placentae, thereby designated as steroid sulphatase deficient. Net hydrolysis of DOCSO4− by the preparations of normal tissue was 9–52 fmol; hydrolysis of this substrate by steroid sulphatase-deficient tissues was indistinguishable from that by boiled tissue (< 29 fmol). Thus preparations of placentae which hydrolysed DHASO4− also hydrolysed DOCSO4− ; tissues which did not hydrolyse DHASO4− also failed to hydrolyse DOCSO4−.

The quantities of DHASO4− and DOCSO4− hydrolysed by the 28 individual placentae showed a positive correlation (r = 0·91, P < 0·001). The apparent Michaelis constants for hydrolysis of DHASO4− and DOCSO4− were 38 and 274 μmol/l respectively.

These results are consistent with the proposal that these substrates are hydrolysed by a common enzyme.

J. Endocr. (1985) 106, 295–301
Functional development of the oxytocin release mechanism and its role in the initiation of parturition in the rat
Authors: Higuchi T. , Uchide K. , Honda K. , Negoro H.
Published: December 2008

Developmental changes in levels of oxytocin in the blood and the pituitary gland and in oxytocin responses to oxytocin-releasing stimuli were investigated in the rat from the fetus close to term to the 40-day-old young adult. The oxytocin content of the pituitary gland rose gradually from fetuses of 21 days of gestation to 40-day-old rats. Pituitary oxytocin levels expressed in terms of body weight also increased up to day 25 after birth and declined slightly thereafter. In contrast, serum concentrations of oxytocin increased from day 21 of pregnancy up to day 5 after birth but were stable thereafter. Oxytocin levels in both blood and the pituitary gland were equal in 23-day-old fetuses and 1-day-old infants born on day 22 of pregnancy. There was no difference in serum and pituitary oxytocin levels in newborn pups and unborn littermates of day 22 or 23 of gestation. The i.p. injection of hypertonic saline induced a significant increase in serum oxytocin levels on day 5 and later, but no effect in the fetus on day 22 of gestation and in the 1-day-old infant. The responsiveness to the osmotic stimuli increased after 5 days of age. The i.p. injection of diethyl-dithiocarbamate, a noradrenaline synthesis inhibitor, or phenobarbitone was effective in raising blood oxytocin levels only in rats older than 10 and 20 days of age respectively. These findings, that a gradual increase in oxytocin levels in both blood and the pituitary gland without an apparent increase in its release and the absence of a pituitary response to oxytocin-releasing stimuli during the perinatal period, do not support a role for fetal oxytocin in the initiation of labour in the rat.

J. Endocr. (1985) 106, 311–316
Evidence for a spinal site at which opioids may act to inhibit the milk-ejection reflex
Authors: Wright D. M.
Published: December 2008

Morphine was injected into the lumbar subarachnoid space of anaesthetized lactating rats (7–10 days post partum) to examine its effect on the milk-ejection reflex at a spinal level. Although the delay until the first milk-ejection response to the suckling of hungry pups was variable (3–60 min) the subsequent responses occurred at regular intervals of 7·5± 0·4 min; milk-ejection responses were detected by measurement of intramammary pressure and by the characteristic behaviour of the pups. Injection of morphine (4–50 μg) via a cannula inserted into the spinal subarachnoid space inhibited reflex milk ejection in a dose-related manner without affecting the sensitivity of the mammary gland to exogenous oxytocin (1 mu., i.v.); injection extradurally was without effect. The opiate antagonist naloxone (10 μg), when injected intrathecally, did not significantly alter the pattern of reflex milk ejection or the amplitude of the intramammary pressure response, but prevented the inhibitory effect of morphine when administered with the opiate. Pethidine (250 and 400 μg) also inhibited the milk-ejection reflex.

It is unlikely that the effect of spinal administration of morphine occurred as the result of the transportation to a supraspinal site since release of oxytocin evoked by intraventricular injection of hypertonic sodium chloride (3 mol/l) was blocked by intraventricular injection of morphine (4 μg) but not by a much larger dose (40 μg) injected intrathecally.

J. Endocr. (1985) 106, 401–407
CATECHOL OESTRADIOL CONTROL OF FSH-STIMULATED GRANULOSA CELL STEROIDOGENESIS
Authors: Hudson K.E. , Hillier S.G.
Published: December 2008

Catechol oestrogens are formed in the ovary but it is not known if they have a local function. Working with primary granulosa cell cultures prepared from immature rat ovaries, we found that the presence of 2-hydroxyoestradiol in the culture medium (48 h incubation) dramatically enhanced the steroidogenic response (progesterone production) to human FSH (100 ng/ml). The effect of 2-hydroxyoestradiol was dose-dependent and maximal (approximately 40 times the response to FSH alone) at 3.0 μM. The stimulatory action of 1.0 μM 2-hydroxyoestradiol was >10 times more than that of 1.0 μM oestradiol but only half that of 1.0 μM testosterone; other catechol oestrogens (2-hydroxyoestrone, 4-hydroxyoestradiol, 2-methoxyoestradiol and 2-methoxyoestrone) were not stimulatory. The stimulatory actions of 2-hydroxyoestradiol and testosterone were partially additive and each was antagonized in the same way by the presence of a specific antiandrogen (SCH16423). These observations suggest a role for intrafollicular catechol oestradiol in modulating FSH-stimulated granulosa cell steroidogenesis; its mechanism of action may be similar to that of testosterone.
CORTISOL IS NATRIURETIC IN THE IMMATURE OVINE FETUS.
Authors: Wintour E.M. , Coghlan J.P. , Towstoless M.
Published: December 2008

Cortisol was infused, intravenously, for 4 h continuously into 5 chronically cannulated ovine fetuses at 111-120 days of gestation (term is 142-152 days). The dose used was 100 μg/h, and raised fetal blood cortisol concentrations from 8.2±4.0 to 56.5±19.0 nmol/l (values are mean ± SEM). The effects observed were 1) a 4-5 fold increase in sodium and chloride excretion, 2) a doubling of potassium excretion and free water clearance, 3) no significant changes in urine pH, urea and creatinine excretions, and 4) an increase in urine osmolality from 129±7.5 to 154.4±11.3 mosmol/kg water. There were no significant changes in any of the measured parameters in 5 fetuses infused with 0.9% NaCl for 4 h. It is suggested that the hyponatremia and inability to retain sodium observed in many premature or very low birth weight babies may be due to the fact that their kidneys are behaving as fetal rather than neonatal organs and responding to the high plasma cortisol concentrations found in such babies with a natriuresis.
Electrical responses of cultured porcine thyroid cells to adrenergic agents
Authors: McGrath P. A. , Bourke J. R. , Huxham G. J. , Manley S. W.
Published: December 2008

The membrane potential of cultured porcine thyroid follicular cells depolarized by up to 20 mV from the resting value of about − 73 mV on exposure to β-adrenoceptor agonists. A similar response was induced by TSH or dibutyryl cyclic AMP. α-Adrenoceptor agonists were without effect. The receptor subtype was shown to be (at least predominantly) β2 by the order of potency for β-agonists (isoprenaline ≅ fenoterol⪢adrenaline >noradrenaline) and by the relative potency of selective β-antagonists (ICI 118,551 ⪢atenolol). The α-agonist phenylephrine had no effect on the TSH response but weakly inhibited the β-agonist response. Rather than a physiological antagonism between α- and β-adrenoceptor-mediated responses, this effect was shown to be due to the weak β-antagonist effect of phenylephrine since the α-antagonist phentolamine failed to potentiate the depolarizing response to the mixed agonist nor-adrenaline, and also failed to block the inhibitory action of phenylephrine on the β-agonist effect. Sensitivity to β-agonist was enhanced by omission of serum from the culture medium and reduced by exposure to β-agonists or a high concentration of TSH or dibutyryl cyclic AMP.

J. Endocr. (1985) 107, 23–30
Pituitary gonadotrophin-releasing hormone receptor up-regulation in vitro: dependence on calcium and microtubule function
Authors: Young L. S. , Naik S. I. , Clayton R. N.
Published: December 2008

Exogenous cyclic adenosine nucleotides increase gonadotrophin-releasing hormone (GnRH) receptors in intact cultured rat pituitary cells in a similar manner to that observed with GnRH itself. In this study the calcium and microtubule dependency of GnRH receptor up-regulation was examined in vitro. Treatment of pituitary cells in Ca2+ and serum-containing media with either GnRH (1 nmol/l), K+ (58 mmol/l) or dibutyryl cyclic AMP (dbcAMP; 1 mmol/l) for 7–10 h routinely resulted in a 50–100% increase in GnRH receptors. Incubation of pituitary cells with the calcium channel blocker verapamil, for 7 h, or the calcium chelator EGTA, for 10 h, had no effect on basal receptor levels but prevented the increase in GnRH receptors stimulated by either GnRH, K+ or dbcAMP. Luteinizing hormone release measured with the same stimulators over a 3-h period was prevented by both verapamil and EGTA. Calcium ionophore (A23187) increased GnRH receptors by 40–60% at low concentrations (10 and 100 nmol/l) while higher concentrations (10 and 100 μmol/l) reduced receptor levels. Luteinizing hormone release was not increased by receptor-stimulating concentrations of A23187, but was by higher concentrations (10 μmol/l). None of these pretreatments, for up to 10 h, impaired the subsequent LH response of the cells to increasing doses of GnRH.

Vinblastine (1 μmol/l did not affect basal receptor levels but markedly reduced the increase in GnRH receptors stimulated by GnRH, K+ and dbcAMP. This concentration of vinblastine had no effect on LH release. These results indicate that receptor stimulation by GnRH, K+ and dbcAMP is a calcium-dependent process requiring the integrity of the microtubule system and there is a different calcium requirement for the processes of GnRH receptor up-regulation and LH secretion.

J. Endocr. (1985) 107, 49–56
Cortisol kinetics and fluid distribution in brook trout (Salvelinus fontinalis)
Authors: Nichols D. J. , Weisbart M. , Quinn J.
Published: December 2008

Cortisol kinetics were examined in brook trout (Salvelinus fontinalis) to assess possible relationships with body fluid distribution during acclimation to sea water (SW). The disappearance curve of [3H]cortisol in plasma, after a bolus injection, was analysed by compartmental analysis using a three-pool mammillary model. The results indicated that only ∼ 10% of the total exchangeable cortisol was located in the plasma pool. Over 75% of the total cortisol was associated with a large slowly exchanging pool and the remaining cortisol was located in a second extravascular tissue pool which was in rapid exchange with the plasma pool.

Two days after transfer of trout from fresh water to SW, when plasma chloride concentration was at a new steady state, body weight, intracellular fluid volume, haematocrit and inulin clearance rate were lowered but plasma, blood and extracellular volumes were unaltered. Cortisol plasma clearance rate was unaltered but plasma cortisol concentration, cortisol secretion rate, total cortisol pool size and interpool transport rates were increased. These results are consistent with an acute role for cortisol in SW adaptation of brook trout.

The fraction of the total cortisol cleared was smaller and the average time that cortisol spent in the tissue pools was slightly longer in trout after transfer to SW, possibly reflecting altered fluid dynamics. The fractional disappearance rate was larger at higher plasma cortisol concentrations in the SW trout. This relationship is compatible with the hypothesis that cortisol protein binding protects cortisol from metabolism.

J. Endocr. (1985) 107, 57–69
Single nephron function during prolactin-induced pseudopregnancy in the rat
Authors: Walker J. , Garland H. O.
Published: December 2008

Whole kidney and renal micropuncture techniques were used to investigate the effects of chronic prolactin treatment on kidney function in anaesthetized female rats. At the whole kidney level, glomerular filtration rate (GFR) and fluid reabsorption were both significantly (P<0·02) increased in the hormone-treated group. At the single nephron level, GFR and proximal fluid reabsorption were also increased (P<0·05) by prolactin treatment. Fractional reabsorption was also enhanced at the proximal tubular level in hormone-treated animals. Such changes in renal function are similar to those seen in rat pregnancy and cervically stimulated pseudopregnancy. Since circulating prolactin concentrations are increased in both reproductive states, the hormone may play an important role in establishing the characteristic renal changes seen therein.

J. Endocr. (1985) 107, 127–131
Characterization of a specific insulin-like growth factor-I/somatomedin-C receptor on high density, primary monolayer cultures of bovine articular chondrocytes: regulation of receptor concentration by somatomedin, insulin and growth hormone
Authors: Watanabe N. , Rosenfeld R. G. , Hintz R. L. , Dollar L. A. , Smith R. L.
Published: December 2008

In order to obtain a phenotypically stable cell population of chondrocytes, high density primary monolayer cultures of bovine articular chondrocytes were established. Using these cultures, a specific insulin-like growth factor-I/somatomedin-C (IGF-I/SM-C) receptor was demonstrated and characterized. At 15 °C steady-state binding was attained by 5 h, and averaged 25% per 2·2 × 106 cells. Fifty per cent displacement of 125I-labelled IGF-I/SM-C by unlabelled IGF-I/SM-C occurred at concentrations of only 2·3 ng/ml, whereas IGF-II and porcine insulin were approximately 15-and 1000-fold less potent respectively. Scatchard analysis gave a linear plot, with a calculated association constant of 2·26 × 109 l/mol and a receptor number of 15 400 sites per cell.

Preincubation of chondrocyte monolayers with either IGF-I/SM-C or porcine insulin at 37 °C for 20 h resulted in reduction of 125I-labelled IGF-I/SM-C binding in a dose-dependent manner, although higher concentrations were required with insulin. More than 40% down-regulation of the receptor occurred with IGF-I/SM-C at concentrations of 10 nmol/l and nearly 70% reduction at 50 nmol/l. Interestingly, after preincubation with either human (h) or bovine (b)GH, 40% down-regulation of 125I-labelled IGF-I/SM-C binding was observed at concentrations of 10 μmol/l. Local production of IGF-I/SM-C by chondrocytes in response to GH stimulation may have occurred, but, because only 120 pmol IGF-I/SM-C and < 30 pmol IGF-I/SM-C per litre were recovered from serum-free conditioned media preincubated with bGH and hGH respectively, this was not established.

These studies demonstrate that cultured bovine articular chondrocytes possess a highly specific IGF-I/SM-C receptor, and that this receptor population is regulated not only by IGF-I/SM-C and insulin but also by high concentrations of either hGH or bGH. These results are consistent with the growth-promoting action of IGF-I/SM-C on skeletal tissues, and suggest the possibility that GH itself may play its own role to modulate IGF-I/SM-C receptors on chondrocytes.

J. Endocr. (1985) 107, 275–283
Vasopressin secretion as a possible target of the γ-aminobutyric acid-mediated component of the corticosteroid feedback effect
Authors: Ács Zs. , Lutz-Bucher B. , Koch B. , Stark E.
Published: December 2008

The inhibition of γ-aminobutyric acid (GABA) synthesis did not interfere with the suppressive effect of dexamethasone on the stress-induced rise of plasma corticosterone levels in vasopressin-deficient homozygous Brattleboro rats. In dexamethasone-treated heterozygous rats corticosterone and vasopressin secretion increased after stress provided GABA synthesis was inhibited. The results indicate that inhibition of corticotrophin secretion by corticosteroids may in part be mediated by enhancement of GABA synthesis and a consequent inhibition of vasopressin release.

J. Endocr. (1985) 107, 303–307
Increased sensitivity of the osmotic control of vasopressin in sheep with deoxycorticosterone acetate-induced hypertension
Authors: Brooks D. P. , Share L. , Crofton J. T. , Guthe C. , Ling W. D. , Bohr D. F.
Published: December 2008

The development of hypertension induced by deoxycorticosterone acetate (DOCA) in sheep was accompanied by increases in both the plasma concentration and the urinary excretion of vasopressin. The vasopressin response to an osmotic stimulus (i.v. infusion of 0·85 mol NaCl/l at 4 ml/min for 75 min) was studied before and after the development of hypertension induced by DOCA in six sheep. Before DOCA implantation, the osmotic stimulus resulted in an increase of plasma osmolality (POSM) from 290 ± 1 to 303 ± 1 (s.e.m.) mosmol/kg H2O and in plasma vasopressin concentration (PAVP) from 0·23 ± 0·04 to 1·07 ± 0·15 μu./ml. At least 30 days after DOCA implantation when mean arterial blood pressure had risen from 81 ± 3 to 117 ± 5 mmHg, the same osmotic load caused an increase in POSM from 290 ± 2 to 298± 2 mosmol/kg H2O and PAVP from 0·45 ± 0·05 to 2·02 ± 0·27 μu./ml. POSM and PAVP were significantly correlated in every experiment. However, the slope of the relationship increased significantly (P<0·01) after the animals had developed hypertension (0·185± 0·026 vs 0·070 ± 0·011 (μu. vasopressin/ml)/(mosmol/kg H2O)). The intercepts were similar. After the DOCA implant had been removed osmotic sensitivity returned to normal.

J. Endocr. (1985) 107, 309–315
Regulation of testosterone production in Leydig cells from fetal mice under dynamic conditions: effect of human chorionic gonadotrophin and 8-bromo-cyclic AMP
Authors: Pointis G. , Latreille M. T.
Published: December 2008

The temporal release of testosterone by Leydig cells from 18-day-old mouse fetuses in response to human chorionic gonadotrophin (hCG) and to 8-bromo-cyclic AMP (8-bromo-cAMP) was investigated under short-term incubation (180 min) conditions. A rapid and large increase in testosterone release was induced by a 5-min exposure to hCG (20 i.u./l) or 8-bromo-cAMP (10 mmol/l). The testosterone response of fetal Leydig cells to the two gonadotrophic stimuli was Gaussian in distribution with a peak value of testosterone by 15–20 min. Repeated exposure to hCG resulted in a reduced testosterone response but an increased accumulation of cAMP. The apparent resistance of fetal Leydig cells to hCG could not be overcome either by increasing the hCG concentration (to 2000 i.u./l) or by exposing the cells to 8-bromo-cAMP (10 mmol/l). Continuous exposure to hCG (200 i.u./l) divided into multiple small doses (each 8 i.u./l) induced testosterone secretion with different kinetic characteristics: a three-fold longer time-lag between hormone exposure and the peak value; a twofold greater testosterone response (P<0·001) and a gradual decrease of testosterone secretion. Oestradiol significantly reduced basal and hCG-stimulated testosterone production only at a high concentration (10 μmol/l). These results indicate that continuous or pulsatile exposure to hCG can induce refractoriness of fetal Leydig cells. The similarity between the actions of hCG and 8-bromo-cAMP on fetal steroidogenesis suggests that this rapid defect is not primarily due to a depletion of gonadotrophin receptors but results from disruption of regulatory mechanisms at the post-receptor level.

J. Endocr. (1985) 107, 409–414
Seasonal influence on thyroidal response to thyrotrophin-releasing hormone in cattle and buffaloes
Authors: Khurana M. L. , Madan M. L.
Published: December 2008

The effect of thyrotrophin-releasing hormone (TRH) on the circulating plasma levels of tri-iodothyronine (T3) and thyroxine (T4) was determined in the same group of animals (four cattle and four Murrah buffaloes) during hot dry (HD), hot humid (HH) and cold environmental conditions. Plasma T3 and T4 concentrations were measured during 2 h before and up to 12 h after the administration of TRH (200 μg i.v.). In the preinjection period in both cattle and buffaloes T3 levels were significantly lower in HH conditions. No significant difference in basal (preinjection) T3 levels was observed during HD and cold seasons in cattle. The highest T3 levels were obtained in buffaloes during HD season with intermediate values during the cold months. Plasma T4 levels in these animals were reversed during HD and HH months. In both cattle and buffaloes there was a biphasic response of T3 and T4 to TRH treatment and this varied with time and in size. The season significantly affected the T3 response to TRH in cattle and buffaloes but the T4 response differed in the two species. The ratio of T4/T3 was higher during HH condition compared with other seasons in both cattle and buffaloes. The climate significantly affected the thyroidal response to TRH.

J. Endocr. (1986) 108, 57–61
Oestriol and non-protein-bound oestriol concentrations in human peripheral plasma before labour and delivery
Authors: Moutsatsou V. , Oakey R. E.
Published: December 2008

The concentration of oestriol and the proportion of this hormone not bound to plasma protein were measured using radioimmunoassay and centrifugal ultrafiltration respectively, in 55 samples of plasma obtained from 12 women in the last 2 to 7 weeks of uncomplicated pregnancy. Among individuals, the mean plasma concentration of oestriol varied from 25·8 to 94·8 nmol/l; in nine subjects, there was a tendency for oestriol concentrations to increase as delivery approached. The mean proportion of oestriol not bound to plasma protein in the different subjects varied from 13·1 to 18·9%, but values from any individual subject remained essentially constant during the periods of study. These measured values were used to calculate, for each sample, the apparent concentration of oestriol not bound to plasma protein. The results were combined with analogous values for oestradiol and progesterone obtained from the same plasma samples and described in a previous study. It was found that (i) the mean ratio of the concentration of oestriol and oestradiol was 0·75, (ii) the mean concentration of non-protein-bound oestriol was 8·7 times that of non-protein-bound oestradiol, and (iii) in individual subjects, there was no consistent trend as delivery approached in the ratio of the concentration of progesterone to that of oestriol in either the total or non-protein-bound form.

J. Endocr. (1986) 108, 75–80
Ontogeny and oestradiol dependence of vitamin D-binding protein blood levels in chickens
Authors: Nys Y. , Bouillon R. , Van Baelen H. , Williams J.
Published: December 2008

The concentration of 25-hydroxyvitamin D3-binding protein (DBP) was measured, by immunodiffusion, in the blood of chickens from embryonic stages to sexual maturity. Low levels of DBP and 1,25-(OH)2D3 were detectable in the blood of chick embryos from the 12th and 17th day of incubation respectively and stayed at the same low levels until hatching. The blood concentration of DBP doubled between the 1st and 5th days of life, then increased slowly and reached the mean level of the adult male at 7–8 weeks of age. The concentration of DBP was independent of vitamin D status in growing chickens. A large increase was observed in DBP blood levels in hens just before sexual maturity. This change, and those observed in moulting hens, followed the variations in plasma concentrations of oestradiol more closely than those of progesterone or testosterone. Moreover, a large increase in plasma DBP levels was induced in immature chickens by oestradiol (0·5 mg/day), but not by testosterone or progesterone. Finally, the experimental suppression of egg shell formation and the associated decrease in 1,25-(OH)2D3 plasma levels had no effect on plasma DBP concentrations. However, 1,25-(OH)2D3 and DBP levels were higher in hens laying shell-less eggs than in immature pullets. The increases in DBP levels at hatching, in immature pullets treated with oestrogens, in hens laying uncalcified eggs and at the onset of egg production were associated with increases in 1,25-(OH)2D3, suggesting a relationship between the levels of DBP and 1,25-(OH)2D3 in the blood.

J. Endocr. (1986) 108, 81–87
Testosterone maintains pituitary and serum FSH and spermatogenesis in gonadotrophin-releasing hormone antagonist-suppressed rats
Authors: Rea M. A. , Marshall G. R. , Weinbauer G. F. , Nieschlag E.
Published: December 2008

Groups of adult male rats were treated continuously for 30 days with either vehicle or the potent gonadotrophin-releasing hormone (GnRH) antagonist, (N-Ac-d-Nal(2)1,d-pCl-Phe2,d-Trp3,d-hArg (Et2)6,d-Ala10)-GnRH (RS 68439; 35 μg/day). In addition, groups of vehicle- and antagonist-treated rats received s.c. testosterone implants sufficient to maintain serum testosterone concentrations 3·5- to 5-fold higher than those of vehicle-treated control rats. After 30 days of antagonist treatment serum LH, FSH and testosterone concentrations were at or below the detection limits of their respective assays and pituitary FSH content and GnRH receptor binding were reduced, relative to control animals, by 77 and 98% respectively. Testis weight in antagonist-treated rats was reduced by 75% and spermatogenesis was suppressed to an extent comparable to that observed in hypophysectomized rats. Testosterone, which caused a 40% reduction in serum FSH relative to control animals, prevented the antagonist-induced fall in both serum and pituitary FSH, but not GnRH receptors, below that observed in the vehicle plus testosterone-treated group. Furthermore, spermatogenesis in the antagonist plus testosterone-treated group was indistinguishable from that observed in control animals. It is concluded that testosterone is capable of maintaining serum and pituitary FSH levels in vivo, under conditions which presumably render the pituitary insensitive to hypothalamic GnRH.

J. Endocr. (1986) 108, 101–107
Comparison of particle-associated progesterone and oxytocin in the ovine corpus luteum
Authors: Rice G. E. , Jenkin G. , Thorburn G. D.
Published: December 2008

The subcellular distribution of progesterone and oxytocin within the ovine corpus luteum was investigated using differential and density gradient centrifugation. Progesterone and oxytocin were associated with particles which sedimented to a density of 1·049–1·054 g/ml and 1·054–1·061 g/ml respectively. Particle-associated progesterone did not, however, display physical or biochemical characteristics consistent with its storage within secretory granules. When particle-associated progesterone was incubated in HEPES buffer at 37 °C, 70% of the total progesterone was recovered in the incubation medium. The remaining stable particle-associated progesterone was not affected by treatments which stimulated oxytocin release and which have been shown to cause the release of peptides and biogenic amines from secretory granules. These results suggest that particle-associated progesterone represents the intercalation of progesterone into cell membranes and they do not support the hypothesis that progesterone is stored, in a protein-bound form, in luteal secretory granules.

J. Endocr. (1986) 108, 109–116
A novel pituitary protein (7B2)-like immunoreactivity is secreted by a rat phaeochromocytoma cell line (PC12)
Authors: Suzuki H. , Tischler A. S. , Christofides N. D. , Chretien M. , Seidah N. G. , Polak J. M. , Bloom S. R.
Published: December 2008

High concentrations of a novel pituitary protein (7B2) have been shown to be present in the PC12 rat phaeochromocytoma cell line by radioimmunoassay. 7B2-like immunoreactivity (IR-7B2) was released from PC12 cells into the incubation medium in response to stimulation by a depolarizing concentration of K+, and this K+-evoked release was inhibited by Co2+, The major IR-7B2 in PC12 cell and medium appeared to be identical to that in porcine pituitary gland as judged by both gel permeation chromatography and by reverse-phase high performance liquid chromatography (HPLC). Gel permeation chromatography of extracts of cell and medium revealed two IR-7B2 peaks, the earlier eluting at a elution coefficient (Kav) of 0·30 and the later at a Kav of 0·54. In medium, over 90% of the IR-7B2 eluted as the earlier peak. Fractionation of extracts of cell and medium on reverse-phase HPLC showed three main IR-7B2 peaks eluting at 43, 44·5 and 46% acetonitrile/water with 0·1% trifluoroacetic acid. The findings suggest that IR-7B2 might be released by calcium-mediated exocytosis.

J. Endocr. (1986) 108, 151–155
Vasopressin and oxytocin responses to acute and chronic osmotic stimuli in man
Authors: Williams T. D. M. , Abel D. C. , King C. M. P. , Jelley R. Y. , Lightman S. L.
Published: December 2008

The regulation of both arginine vasopressin (AVP) and oxytocin secretion was studied during rapid and prolonged osmotic stimuli in normal adult volunteers. In five subjects given an intravenous infusion of 0·85 mol NaCl/l at 0·05 ml/kg per min over 2 h there was a significant (P<0·05) rise only in plasma AVP, with no significant change in plasma levels of oxytocin. In six further subjects 5 days of restriction to 500 ml fluid daily resulted in significant increases of both plasma and 24-h urinary AVP, whereas there was no change in corresponding oxytocin levels. During another 5-day period in which the same subjects were given an additional 200 mmol sodium as well as having their fluid intake restricted to 1000 ml daily, there were again significant rises in plasma and 24 h urinary AVP with no change in corresponding oxytocin levels. We conclude that, in man, AVP is selectively secreted in response to both dehydration and high sodium intake, whilst even after the stimulus of rapidly increasing plasma osmolality during intravenous infusion of hypertonic saline the rise in oxytocin is not statistically significant. It therefore appears unlikely that oxytocin has a significant role in the physiological control of fluid balance in man.

J. Endocr. (1986) 108, 163–168
Urine pH and the relationship between urine flow and urinary prostaglandin E excretion in the rat
Authors: Haylor J. , Lote C. J.
Published: December 2008

The relationship between urine flow and urinary prostaglandin E (PGE) excretion was investigated at constant urine pH in the anaesthetized rat. The urine pH was maintained at approximately pH 6 or pH 8 by the intravenous infusion of either ammonium chloride or sodium bicarbonate respectively.

Two distinct patterns in the relationship between PGE excretion and urine flow were observed. The first showed a fall in urinary PGE excretion as the urine flow increased over the low flow range of 2–5 ml/h, and was common to both experiments. The second relationship, however, showed a marked difference between the ammonium chloride and sodium bicarbonate experiments since: (a) in acidic urine (pH 6), PGE excretion increased (P < 0·002) with the urine flow, attaining a rate of 87± 6 pmol/h (n = 6) at the highest level of flow achieved (12 ml/h); (b) in alkaline urine (pH 8), PGE excretion was significantly (P < 0·01) higher but did not increase with urine flow, remaining constant at approximately 90 pmol/h (n = 6).

The lack of any additive effect on urinary PGE excretion between increasing the urine flow and making the urine alkaline may be explained by both stimuli acting through a common mechanism, a concept which is consistent with the hypothesis that PGE may be reabsorbed in the distal nephron. The flow-dependency of urinary PGE excretion could therefore result from a reduction in reabsorption rather than the increase in passive secretion proposed previously. In addition, PGE excretion in alkaline urine may be a more appropriate index of renal PGE synthesis, since above a urine pH of 7·5 its excretion is independent of both urine pH and urine flow.

J. Endocr. (1986) 108, 247–253
Effects of vasopressin-glycine and vasopressin-glycine-lysine-arginine on renal function in the rat
Authors: Lote C. J. , McVicar A. J. , Smyth D. G.
Published: December 2008

The peptides vasopressin-Gly and vasopressin-Gly-Lys-Arg occur as part of the sequence of the vasopressin-neurophysin precursor molecule and may be released from the hypothalamus and/or pituitary. [8-Lysine]-vasopressin-Gly (LVP-Gly) and [8-lysine]-vasopressin-Gly-Lys-Arg were administered i.v. to conscious, water-diuretic rats. The renal effects of the peptides were assessed by comparison with the actions of [8-lysine]-vasopressin (LVP) which was administered to separate groups of rats.

LVP-Gly and LVP-Gly-Lys-Arg were weakly antidiuretic. LVP-Gly-Lys-Arg was the more potent of the two peptides, but on a molar basis it only had about 10% of the antidiuretic activity of LVP. LVP-Gly and LVP-Gly-Lys-Arg at 10 pmol/h per 100 g body weight (equivalent to the maximal antidiuretic dose of LVP) slightly decreased (P < 0·001) urine flow without causing significant changes in urine osmolality.

LVP (10 pmol/h per 100 g body weight) promoted a marked natriuresis (P < 0·001 ) but LVP-Gly and LVP-Gly-Lys-Arg were not natriuretic, even at the dose which was markedly antidiuretic (100 pmol/h per 100 g body weight). Osmolal output decreased at all doses during administration of the extended peptides, but was not significantly changed in the control group or by LVP. Inulin clearance was decreased by about 30% during administration of both LVP and LVP-Gly-Lys-Arg at 100 pmol/h per 100 g body weight.

It is concluded that LVP-Gly and LVP-Gly-Lys-Arg show weak antidiuretic activities and that the effect on urine flow may be partly due to a decrease in glomerular filtration rate (GFR). The decrease in osmolal output produced by the peptides is also a likely consequence of an effect on GFR. It is suggested that LVP-Gly and LVP-Gly-Lys-Arg have a low potential for activation of tubular vasopressin receptors, as shown by the weak antidiuretic activity and lack of a natriuretic action, but that they have a relatively stronger action on glomerular vasopressin receptors.

J. Endocr. (1986) 108, 255–260