bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of tri-iodothyronine, cortisol and transcriptional inhibitors on vitamin D3-enhanced thyrotrophin secretion by rat pituitary cells in vitro
Authors: d'Emden M. C. , Wark J. D.
Published: December 2008

The hormone 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to selectively enhance agonist-induced TSH release in the rat thyrotroph in vitro. The interaction of 1,25-(OH)2D3 with tri-iodothyronine (T3) and cortisol was studied in primary cultures of dispersed anterior pituitary cells. TRH (1 nmol/l)-induced TSH release over 1 h was enhanced by 70% (P<0·01) following exposure to 10 nmol 1,25-(OH)2D3/l for 24 h. Pretreatment with T3 (1 pmol/l–1 μmol/l) for 24 h caused a dose-dependent inhibition of TRH-induced TSH release. Net TRH-induced TSH release was inhibited by 85% at T3 concentrations of 3 nmol/l or greater. Co-incubation with 1,25-(OH)2D3 resulted in enhanced TRH-induced TSH release at all T3 concentrations tested (P<0·001). The increment of TRH-induced TSH release resulting from 1,25-(OH)2D3 pretreatment was equivalent in the presence or absence of maximal inhibitory T3 concentrations. At 1 nmol T3/1, there was a two- to threefold relative increase in 1,25-(OH)2D3-enhanced TRH-induced TSH release. Incubation with cortisol (100 pmol/l–100 nmol/l) had no effect on basal or TRH-induced TSH release, nor did it alter 1,25-(OH)2D3-enhanced TRH-induced TSH release when added 24 h before, or at the time of addition of 1,25-(OH)2D3. Actinomycin D and α-amanitin abolished 1,25-(OH)2D3-enhanced TSH secretion.

These data demonstrate that the action of 1,25-(OH)2D3 in the thyrotroph required new RNA transcription, and was not affected by cortisol. In the presence of T3, the response of the thyrotroph to TRH induced by 1,25-(OH)2D3 was increased. We have shown that 1,25-(OH)2D3 has significant effects on the action of TRH and T3 in vitro. These findings support the proposal that 1,25-(OH)2D3 may modulate TSH secretion in vivo.

Journal of Endocrinology (1989) 121, 451–458
Indomethacin inhibits the effects of oestrogen in the anterior pituitary gland of the rat
Authors: Rosental D. G. , Machiavelli G. A. , Cherñavsky A. C. , Speziale N. Sterin , Burdman J. A.
Published: December 2008

Two inhibitors of prostaglandin synthesis, indomethacin and aspirin, blocked the increase of oestrogen-binding sites in the nuclear subcellular fraction, an increase which occurs after the administration of oestradiol. Consequently the biological effects of oestrogens in the anterior pituitary gland of the rat (prolactin synthesis, concentration of progesteronebinding sites and cell proliferation) are diminished. The anterior pituitary gland synthesized prostaglandin F2α (PGF2α), PGE2 and PGD2 from arachidonic acid. This synthesis was blocked when indomethacin was added to the culture media. Oestrogen increased the concentration of PGE2: an increase that was partially prevented by indomethacin. Prostaglandins may have an important role on the effects of oestrogen in the anterior pituitary gland of the rat.

Journal of Endocrinology (1989) 121, 513–519
THE CIRCADIAN RHYTHM OF INTACT PARATHYROID HORMONE (1-84) AND NEPHROGENOUS CYCLIC ADENOSINE MONOPHOSPHATE IN NORMAL MEN
Authors: Logue F.C. , Fraser W.D. , O'Reilly D.St.J. , Beastall G.H.
Published: December 2008

A pronounced circadian rhythm has been demonstrated for intact parathyroid hormone (1-84) in the serum of normal male adults. The broad nocturnal rise of parathyroid hormone (1-84) secretion appears to be of physiological significance, for it is accompanied by a significant rise in nephrogenous cyclic adenosine monophosphate. The rate of return of parathyroid hormone (1-84) to baseline concentrations varies between individuals, an observation which has implications for the optimal time of sampling for the investigation of possible mild hyperparathyroidism.
IMMUNOREACTIVE INHIBIN CONCENTRATIONS IN SERUM THROUGHOUT THE MENSTRUAL CYCLE OF THE MACAQUE: SUPPRESSION OF INHIBIN DURING THE LUTEAL PHASE AFTER TREATMENT WITH AN LHRH ANTAGONIST
Authors: Fraser H. M. , Robertson D. M. , De Kretser D. M.
Published: December 2008

Concentrations of immunoreactive inhibin in serum samples collected daily from six adult stumptailed female macaques during normal menstrual cycles were measured with a heterologous radioimmunoassay. Serum inhibin concentrations were low during the follicular phase of the cycle. After ovulation they began to rise, reaching a plateau between 8 and 11 days, before falling in parallel with the decline in luteal progesterone secretion. The dependence of the inhibin secretion by the corpus lutem on pituitary gonadotrophins was investigated by the administration of an LHRH antagonist [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10]LHRH once daily for 3 days beginning on day 8 of the luteal phase in six macaques. LHRH antagonist treatment markedly suppressed serum levels of inhibin and progesterone and these remained at the level found in the follicular phase for the remainder of the luteal phase. These results show that inhibin in the macaque is secreted into the peripheral blood almost exclusively during the luteal phase, being highest when FSH is at its nadir. Suppression of serum inhibin concentrations during the luteal phase by LHRH antagonist suggests that its secretion is integrated with the LH control of the corpus luteum.
Inhibition of neonatal rat growth and circulating concentrations of insulin-like growth factor-I using an antiserum to rat growth hormone
Authors: Flint D. J. , Gardner M. J.
Published: December 2008

Treatment of rats for 24 h on day 2, 10 or 20 of age with a specific antiserum to rGH (anti-(rGH)), GH, bromocriptine (CB-154) or prolactin failed to influence body weight gain or serum concentrations of insulin-like growth factor-I (IGF-I). On day 28 of age, however, anti-(rGH) completely inhibited body weight gain and markedly reduced circulating IGF-I concentrations, effects which were completely prevented by exogenous ovine GH (oGH). When administered to control rats on day 28 oGH caused supranormal weight gain and serum IGF-I concentrations. These results suggested that GH does not play a significant role in growth or regulation of serum IGF-I until after day 20 of age.

By contrast, when anti-(rGH) was given for 4 consecutive days beginning on day 2 of life, body weight gain was reduced within 48 h and remained so until at least 28 days of age. Tail length was also significantly reduced. The effect was due to inhibition of GH effects since serum GH concentrations were low and exogenous GH prevented the effect. Inhibition of growth during the first 14 days of life occurred in the absence of any effect on serum IGF-I although by 21 days of age serum IGF-I was considerably lower than in control rats.

The prolonged reduction in growth after treatment has stopped appeared to be due to a cytotoxic effect on the pituitary gland since pituitary weight and GH but not prolactin content were significantly decreased. The data are consistent with the hypothesis that in the neonate GH may be processed in serum so that a proportion of it is not recognized by an antiserum to pituitary GH.

It would appear that inhibition of GH secretion reduces growth rate by at least 30–40% up to 14 days of age, 50% by 21 days of age and completely by 28 days. Effects of GH on growth could not be fully explained by regulation of serum IGF-I concentrations.

Journal of Endocrinology (1989) 122, 79–86
Cross-reaction of eye muscle antibodies with thyroid tissue in thyroid-associated ophthalmopathy
Authors: Weightman D. , Kendall-Taylor P.
Published: December 2008

The nature of the association of ophthalmopathy with autoimmune thyroid disease is not understood. Serum autoantibodies to eye muscle have previously been identified and in this study we have explored the hypothesis that there may be shared antigenic determinants between orbital and thyroid tissues. Sera were obtained from patients in whom eye muscle antibodies (EMAb) had been detected by an enzyme-linked immunosorbent assay (ELISA); the sera were preincubated with membrane preparations of thyroid or eye muscle, hepatic membranes being used as control. Tissue-binding antibodies were removed from serum by centrifugation and the supernatant serum was analysed using an indirect ELISA and by immunoblotting. In the ELISA, all sera gave a positive response for EMAb. In one serum, the binding was entirely non-specific. All sera showed significant neutralization of EMAb by eye muscle. In six sera there was reduction of EMAb after exposure to thyroidal antigens, indicative of cross-reaction. Western blotting confirmed the non-specific nature of the binding in one serum. In five of the remaining nine sera, protein bands were identified which interacted specifically with eye muscle and, in two of these, the same determinants were neutralized by preincubation with thyroid tissue. The Western blots confirmed the findings in the ELISA. The determinants recognized by IgG were variable between patients and no common antigen could be identified.

This study demonstrates that, in some cases of thyroid-associated ophthalmopathy, there is cross-reaction of EMAb with thyroidal antigens, but this is variable and not found in every case. This may explain the association of the disease with autoimmune thyroid disease, at least in some cases.

Journal of Endocrinology (1989) 122, 201–206
Trypsinization of bovine parathyroid cells abolishes Ca2+-regulated parathyroid hormone secretion
Authors: Muff R. , Fischer J. A.
Published: December 2008

The secretion of parathyroid hormone (PTH) is inversely related to the extracellular Ca2+ concentration (Cae2+). To test the hypothesis that a Ca2+ sensor on the surface of parathyroid cells is involved in Ca2+-regulated PTH secretion, limited trypsinization of bovine parathyroid cells was carried out. Treatment with trypsin (1·1–10 mg/ml) inhibited, in a dose-dependent manner, PTH secretion stimulated by lowering Cae2+ from 2·0 to 0·5 mmol/l. In control cells, activation of protein kinase C with 12-O-tetradecanoylphorbol-13-acetate (TPA) enhanced PTH secretion at 2·0 mmol Cae2+/1 but not at 0·5 mmol Cae2+/1. In trypsinized cells, however, TPA enhanced PTH secretion at both 0·5 and 2·0 mmol Cae2+/1. Isoproterenol-stimulated PTH secretion was maintained in trypsinized cells, but reduced cyclic AMP production revealed that some β-adrenergic receptors were destroyed. The cytosolic free Ca2+ concentration (Cai2+), as measured with fura-2, was raised within seconds in response to increasing Cae2+ from 0·5 to 2·0 mmol/l and was then lowered within 1 min to a sustained plateau; the changes were the same in trypsinized and control cells. In conclusion, trypsinization of parathyroid cells abolished Ca2+-regulated PTH secretion without affecting Cai2+.

Journal of Endocrinology (1989) 122, 213–218
The implication of opiates in the glucocorticoid-mediated inhibition of LH secretion in rats
Authors: Belhadj H. , De Besi L. , Bardin C. W. , Thau R. B.
Published: December 2008

The present study was designed to test the effect of acute administration of dexamethasone on the postcastration and gonadotrophin-releasing hormone (GnRH)-induced rise of LH, and to examine whether the inhibitory action of glucocorticoids on LH secretion was mediated by the opioid system. Rats were castrated and injected 10–10·5 h later in a first set of experiments with saline, dexamethasone (250 μg/rat), nalmefene (2 mg/kg body weight) or nalmefene plus dexamethasone. The response to GnRH was tested 11 h after castration (time 0) in all groups. Dexamethasone caused a significant (P< 0·005) decrease in basal serum concentrations of LH, while saline and nalmefene did not induce any change. The administration of dexamethasone preceded by nalmefene increased basal concentrations of LH (1·6 times), with an effect significantly greater than that of dexamethasone (P< 0·001), nalmefene (P<0·05) or saline (P<0·005) alone. GnRH induced a significant (P < 0·001) increase in serum concentrations of LH in all groups. In a second set of experiments, administration of naloxone (2 mg/kg body weight) increased LH levels (P<0·05) and similarly reversed the inhibitory effect of dexamethasone on LH. These results indicate (1) that the inhibiting effect of dexamethasone on the post-castration rise of LH is likely to be exerted at a suprapituitary level, since dexamethasone does not decrease the GnRH stimulated LH response, (2) that opioid antagonists have the ability to reverse the glucocorticoid-inhibiting effect on LH and (3) that dexamethasone can enhance the effect of nalmefene at a time when serum concentrations of testosterone are at very low levels. We conclude, therefore, that dexamethasone regulates LH secretion, at least in part, through the same pathways as testosterone.

Journal of Endocrinology (1989) 121, 451–456
The anterior pituitary content of neuromedin U-like immunoreactivity is altered by thyrotrophin-releasing hormone and thyroid hormone status in the rat
Authors: Domin J. , Steel J. H. , Adolphus N. , Burrin J. M. , Leonhardt U. , Polak J. M. , Bloom S. R.
Published: December 2008

In this study we have examined the effects of TRH, thyroid hormones and dopamine on the rat anterior pituitary content of neuromedin U-like immunoreactivity. Oral administration of TRH (20 mg/100 g per day) to euthyroid animals evoked a fivefold increase in peptide content after 12 days of treatment. This effect was found to be dependent upon circulating levels of thyroid hormone, since administration of TRH to thyroidectomized animals failed to show a similar effect without simultaneous treatment with tri-iodothyronine. The possibility that the TRH-induced increase in anterior lobe neuromedin U content reflected alterations in prolactin secretion or synthetic rate was also examined. Treatment of euthyroid animals with a dopamine agonist and antagonist was, however, without effect. These results demonstrate a unique relationship between TRH and thyroid hormone levels in increasing the anterior lobe content of neuromedin U immunoreactivity.

Journal of Endocrinology (1989) 122, 471–476
Regulation of insulin-like growth factor-I and growth hormone receptor gene expression by diabetes and nutritional state in rat tissues
Authors: Bornfeldt K. E. , Arnqvist H. J. , Enberg B. , Mathews L. S. , Norstedt G.
Published: December 2008

Insulin-like growth factor-I (IGF-I) mRNA and GH receptor mRNA levels were analysed in different tissues from rats made diabetic with streptozotocin, fasted rats and rats fed with a protein-reduced diet. Diabetes decreased IGF-I mRNA levels in liver, heart, diaphragm, kidney and aorta, but not in brain. GH receptor mRNA levels were decreased in heart and diaphragm, but not in liver and kidney. Fasting decreased IGF-I mRNA in all tissues studied except brain, and decreased GH receptor mRNA in liver, heart and diaphragm, but not in kidney. A protein-reduced diet decreased hepatic IGF-I mRNA levels but did not significantly affect other tissues, while GH receptor mRNA levels were reduced in liver and diaphragm. In conclusion, both diabetes and limited nutrition affected IGF-I and GH receptor mRNA in different tissues, but the two mRNAs were not co-ordinately regulated in all tissues studied. While reduced GH receptor gene expression may thus be responsible for decreased IGF-I gene expression in some states and tissues, additional regulatory mechanisms may be of importance.

Journal of Endocrinology (1989) 122, 651–656
Growth hormone-releasing factor-induced growth hormone secretion from perifused rat anterior pituitary cells: lack of influence of glucose concentration, and normal responses in pituitary cells from diabetic animals
Authors: Caldwell G. , Hart G. , Kohner E. M. , Burrin J. M.
Published: December 2008

The mechanism responsible for the suppression of GH secretion in hyperglycaemia and hypoglyceamia in rats has been investigated using perifusion of anterior pituitary cells. When perifused with Krebs-Ringer bicarbonate containing normal (5 mmol/l), high (20 mmol/l) and low (1 mmol/l) concentrations of glucose, the GH responses to GH-releasing factor (GRF) were 85 ± 5, 85·5 ± 5·4 and 89 ± 3·0 (s.e.m.)% respectively compared with the initial response to GRF at 5 mmol/l in each column. The mean GH response to GRF from anterior pituitary cells of normal rats was 6·58 ± 0·88 μg/three pituitaries, which was not statistically different from that of cells from rats with streptozotocin-induced diabetes (5·40 ± 0·68 μg/three pituitaries). It is concluded that GH suppression in diabetic rats and during hypoglycaemia is not mediated by changes in the GH response to GRF.

Journal of Endocrinology (1989) 122, 657–660
Purification, amino acid sequences and assay cross-reactivities of porcine insulin-like growth factor-I and -II
Authors: Francis G. L. , Owens P. C. , McNeil K. A. , Wallace J. C. , Ballard F. J.
Published: December 2008

Porcine insulin-like growth factor-I (IGF-I) and IGF-II have been characterized to help define the roles of these peptides in the growth process. The amino acid sequence of porcine IGF-I was found to be identical to the human and bovine peptides. Porcine IGF-II was more similar to human IGF-II than to forms of this growth factor in other mammalian species, differing only in the replacement of asparagine for serine at residue 36. In a biological assay that measures the stimulation of protein synthesis in rat L6 myoblasts, porcine IGF-I was approximately ninefold more potent than porcine IGF-II or bovine IGF-II, while recombinant human IGF-I and IGF-II had half the potency of the respective natural peptides. Porcine and recombinant human IGF-I showed essentially equal competition for binding in a human IGF-I radioimmunoassay while between 0·6 and 1·5% cross-reactivity was observed with human, bovine or porcine IGF-II. A receptor assay for IGF-II demonstrated similar potencies for the three IGF-II peptides, while the cross-reactivity of recombinant human IGF-I was only 0·05%. Porcine IGF-I exhibited a higher cross-reactivity, presumably due to very slight contamination with IGF-II.

Journal of Endocrinology (1989) 122, 681–687
Radioimmunoassay of inhibin in various mammals
Authors: Hamada T. , Watanabe G. , Kokuho T. , Taya K. , Sasamoto S. , Hasegawa Y. , Miyamoto K. , Igarashi M.
Published: December 2008

A sensitive radioimmunoassay (RIA) for the determination of inhibin in peripheral plasma and tissue homogenates of different species has been developed using antisera to partially purified bovine follicular fluid (bFF) inhibin and 125I-labelled bFF 32 kDa inhibin. Antisera were produced by immunization of rabbits with partially purified bFF inhibin prepared by immunoaffinity chromatography. Increasing doses of a high titre antiserum could neutralize the suppressing effect of bFF, porcine follicular fluid and rat ovarian homogenate on FSH secretion from rat anterior pituitary cells in culture. Sensitivity of the assay was 3·1 ng International Research Standard of porcine inhibin per tube. Parallel inhibition curves were obtained for inhibin preparations from female and male animals of ten species, i.e. cattle, goats, sheep, cats, dogs, monkeys, pigs, horses, rats and man. Inhibin subunits and related proteins cross-reacted minimally with the antiserum used in the study. Plasma concentrations of inhibin in adult male and female rats were measured by the RIA before and at various times after gonadectomy. Inhibin levels in peripheral plasma before gonadectomy were significantly higher in adult female than in adult male rats. Inhibin levels decreased abruptly after gonadectomy in both sexes and they correlated negatively with plasma concentrations of FSH. This inhibin RIA will facilitate studies of the physiology of inhibin in various species of animals.

Journal of Endocrinology (1989) 122, 697–704
Lesion of the subfornical organ affects the haemotensive response to centrally administered relaxin in anaesthetized rats
Authors: Mumford A. D. , Parry L. J. , Summerlee A. J. S.
Published: December 2008

Experiments were performed on anaesthetized, lactating rats to investigate the acute central actions of relaxin on blood pressure and vasopressin release. When compared with saline and control injections of isotonic protein extract, administration of relaxin into either the lateral or dorsal portion of the third ventricle caused a significant and sustained rise in arterial blood pressure. In contrast, relaxin administered to the ventral portion of the third ventricle caused only a short-term rise in blood pressure. Injections of relaxin into the fourth ventricle were without significant effect, suggesting that the central actions of relaxin on blood pressure are mediated by receptors restricted to the diencephalon or mesencephalon. A similar ventricular specificity was noted for the central relaxin-induced stimulation of vasopressin release as judged by concentrations of the hormone in the peripheral plasma. It is unlikely that the stimulation of vasopressin release is wholly responsible for the observed pressor effect observed.

Lesion of the subfornical organ negated the pressor effect to relaxin injected into the dorsal region of the third ventricle, but did not affect the pressor response observed after injection of relaxin into the ventral portion of the third ventricle. These results demonstrate a biphasic action of centrally administered relaxin, with the response to dorsally placed third ventricle relaxin being mediated by the subfornical organ, and the response to ventral injections associated with an unknown structure of the ventral third ventricle wall.

Journal of Endocrinology (1989) 122, 747–755
Effects of growth hormone-releasing hormone on the secretion of islet hormones and on glucose homeostasis in lean and genetically obese-diabetic (ob/ob) mice and normal rats
Authors: Bailey C. J. , Wilkes L. C. , Flatt P. R. , Conlon J. M. , Buchanan K. D.
Published: December 2008

The effect of synthetic human growth hormone-releasing hormone(1–40) (hGHRH-40) on the function of the endocrine pancreas and on glucose homeostasis in lean and genetically obese-diabetic (ob/ob) mice and normal rats has been examined. The addition of 1 μmol hGHRH-40/1 to incubated islets from normal lean mice increased insulin release by 90 and 37% at 5·6 and 16·7 mmol glucose/l respectively. Lower concentrations of hGHRH-40 did not affect insulin release. hGHRH-40 (1 μmol/l) increased pancreatic polypeptide release by 50% at 5·6 mmol glucose/l. A range of concentrations of hGHRH-40 (1 nmol/l–1 μmol/l) reduced glucagon release by 42–73% at 5·6 mmol glucose/l, and by 38–70% at 16·7 mmol glucose/l. Somatostatin release was increased (eightfold) by 1 μmol hGHRH-40/1 at 5·6 mmol glucose/l, but at 1 nmol hGHRH-40/l somatostatin release was reduced (by > 50%). At 16·7 mmol glucose/litre 0·01–1 μmol hGHRH-40/l increased somatostatin release (three- to fourfold), but 1 nmol hGHRH-40/l produced a reduction of 50%. In vivo, administration of hGHRH-40 (50 μg/kg body weight i.p.) to fasted lean and ob/ob mice did not alter basal plasma concentrations of glucose and insulin, or the glucose and insulin responses to a concomitant i.p. glucose challenge. Intravenous injection of hGHRH-40 (20 μg/kg body weight) to anaesthetized rats increased plasma concentrations of insulin in the hepatic portal vein. A lower dose of hGHRH-40 (0·2 μg/kg) was ineffective, and neither dose of hGHRH-40 altered plasma glucose. The results indicate that hGHRH-40 exerts dose-dependent effects on the secretion of islet hormones, but this does not appear to be sufficient to produce measurable effects on plasma glucose homeostasis.

Journal of Endocrinology (1989) 123, 19–24
Sustained exposure of toxically damaged mouse pancreatic islets to high glucose does not increase β-cell dysfunction
Authors: Eizirik D. L. , Sandler S.
Published: December 2008

The aim of this study was to clarify whether prolonged in-vitro exposure of either normal or damaged β cells to a high glucose environment can be toxic to these cells. For this purpose NMRI mice were injected intravenously with a diabetogenic dose of streptozotocin (SZ; 160 mg/kg) or vehicle alone (controls). Their islets were isolated 15 min after the injection and subsequently maintained in culture for 21 days in the presence of 11·1 or 28 mmol glucose/l. After this period, during acute glucose stimulation, the control islets showed a marked increase in their insulin release in response to a high glucose stimulus. In the SZ-exposed islets there was a decrease in DNA and insulin contents, and a deficient insulin secretory response to glucose. However, in the SZ-damaged islets as well as in the control islets, culture with 28 mmol glucose/l compared with 11·1 mmol glucose/l did not impair islet retrieval after culture, islet DNA content or glucose-induced insulin release. Thus, the degree of damage was similar in the SZ-treated islets cultured at the two concentrations of glucose. These results suggest that glucose is not toxic to normal or damaged mouse pancreatic islets over a prolonged period in tissue culture.

Journal of Endocrinology (1989) 123, 47–51
Sexual maturation in starlings raised on long or short days: changes in hypothalamic gonadotrophin-releasing hormone and plasma LH concentrations
Authors: Dawson A. , Goldsmith A. R.
Published: December 2008

Is the extended prepubertal period which occurs in most birds due to a juvenile photorefractoriness analogous to photorefractoriness in adults? Starlings were taken from nest boxes 4 days after hatching and hand-reared on long days or short days. In females on long days, hypothalamic gonadotrophin-releasing hormone (GnRH) content and plasma LH concentration remained low. In intact males on long days, plasma LH remained low and the testes remained small, and in castrated birds, plasma LH also remained low. In females reared on short days, hypothalamic GnRH content began to increase dramatically from 4 weeks of age and plasma LH increased from 6 weeks of age. In intact males on short days, there was a slight increase in plasma LH and testicular size, and in castrated males, plasma LH increased markedly from six weeks of age. All birds on long days moulted into adult plumage, whereas those on short days retained juvenile plumage. The changes in birds reared on short days were similar to those found when photorefractory adult birds are transferred to short days. This adds to the evidence that juvenile photorefractoriness is analogous to photorefractoriness in adults, and therefore that the seasonal termination of photorefractoriness is an annual puberty. However, the responses to short days occur later in birds raised on short days than in older birds transferred to short days, which suggests either that short day-induced changes occur more slowly in young birds, or that birds only respond to short days after a certain age.

Journal of Endocrinology (1989) 123, 189–196
Acute desensitization of pituitary FSH response to LHRH in ovariectomized rats: further evidence that in the presence of ovarian proteins the LHRH-dependent, LH-like component of FSH release becomes apparent
Authors: Lambalk C. B. , van Rees G. P. , Schoemaker J. , de Koning J. , van Dieten J. A. M. J.
Published: December 2008

Pulsatile release of LHRH and short-term pituitary desensitization to LHRH in the rat are believed to be necessary for the maintenance of LH pulsatility. In contrast, FSH release is partly induced by LHRH release and is partly LHRH-independent. This LHRH-independent release of FSH is subject to inhibitory feedback control by ovarian proteins (probably inhibin), and may obscure an LHRH-induced shortterm loss of pituitary FSH responsiveness to LHRH. The object of this study was to establish whether short-term pituitary desensitization to single doses of LHRH results not only in a loss of LH response, but also of FSH response. Ovariectomized rats were used to eliminate the influence of steroid feedback.

A group of ovariectomized rats was pretreated with steroid-free bovine follicular fluid (bFF) to suppress LHRH-independent FSH release, and phenobarbital to suppress LHRH-dependent FSH release respectively, 7 and 1 h before administration of LHRH. Another group received phenobarbital only. The animals were injected sequentially with either low or high doses of LHRH (1·25 or 10 ng/100 g body weight at times 0 and at 80, 120 or 180 min, and 6·25 or 50 ng/100 g at 60 min). Blood was taken for FSH measurements before and 5 and 10 min after each injection. Rats pretreated with bFF and phenobarbital showed an acute FSH response related to the dose of injected LHRH. No dose–response curve was seen in animals which had only been pretreated with phenobarbital. A significantly attenuated FSH response to LHRH injections of 1·25 or 10 ng/100 g, given 20 min after an injection of 6·25 or 50 ng LHRH/100 g body weight respectively, was observed in animals pretreated with a combination of phenobarbital and bFF, but not in those treated with phenobarbital alone.

The present results confirm that FSH release is under dual control by LHRH and ovarian secretory proteins. When both LHRH-dependent FSH release and the LHRH-independent FSH release are suppressed, short-term desensitization of FSH release to exogenous LHRH can be demonstrated. It is concluded that the phenomenon of short-term pituitary desensitization to LHRH and inhibitory ovarian proteins may both play a role in the regulation of FSH release.

Journal of Endocrinology (1989) 123, 221–226
Maturational changes in the LH response of domestic fowl to synthetic chicken LHRH-I and -II
Authors: Wilson S. C. , Cunningham F. J. , Chairil R. A. , Gladwell R. T.
Published: December 2008

Treatment of chickens at different stages of sexual development with a single i.v. injection of synthetic chicken LHRH (cLHRH)-I or -II stimulated a rise in the plasma concentration of LH within 1 min. The activity of cLHRH-II was 1·3- to 2·7-fold greater than that of cLHRH-I in sexually immature cockerels and hens as determined by the changes in the plasma concentration of LH during the 5 or 10 min after injection. This could be attributed to both a greater effectiveness of cLHRH-II to stimulate LH release and to a more prolonged action. Thus, LH concentrations in plasma were maximal within 1–2 min of injection of all doses of cLHRH-I but within 2–5 min of injection at the higher doses of cLHRH-II. The responsiveness of the pituitary gland to cLHRH-I and -II was substantially greater in the sexually immature cockerel than in the hen and diminished during sexual development of the hen. Coincident with the onset of egg laying, the characteristics of the LH response to cLHRH-II changed to consist of an initial rise during the first 2 min, followed by a more sustained increase with LH concentrations still rising 10 min after injection. In contrast, after injection with cLHRH-I, plasma concentrations of LH rose to a peak at 2 min and thereafter declined gradually. Treatment of the sexually immature hen with oestradiol, progesterone or a combination of both steroids did not enable the expression of a laying hen-type response to the injection of cLHRH-II. It would appear, therefore, that unidentified events associated with the final stages of sexual maturation bring about changes in the mechanism of action of cLHRH-II which differ from those of cLHRH-I.

Journal of Endocrinology (1989) 123, 311–318
Characterization of epidermal growth factor-related proteins from human urinary chorionic gonadotrophin
Authors: Hofmann J. , Hölzel F. , Hackenberg R. , Schulz K.-D.
Published: December 2008

A urinary chorionic gonadotrophin (hCG) preparation, mitogenic for ovarian carcinoma cells, was analysed by gel filtration through Sephadex G-100 Superfine. The resulting fractions were tested for hCG and for properties of the epidermal growth factor (EGF) by radioimmunoassays (RIA) in comparison with their ability to stimulate the growth of EFO27nu ovarian carcinoma cells. The elution profile of the RIA activities for hCG corresponded to molecular weights of 12 and 71 kDa, whereas the mitogenic activity was found in peak fractions eluting at 7, 11 and 52 kDa, indicating the presence of mitogenic substances distinct from hCG or its β-subunit. In comparison experiments, radiolabelled recombinant human EGF eluted at 7 kDa from the column. The profile of EGF immunoreactivity determined in the eluant fractions of hCG preparation A correlated with the mitogenic potential. Eluant fractions with growth-promoting activity competed with 125I-labelled EGF in binding to EFO-27nu cells; the inhibition of EGF binding was correlated with the mitogenic potential and the EGF immunoreactivity. We assume that the 7 kDa component of the gel filtration eluate corresponds to monomeric EGF; the high molecular weight mitogens may represent EGF precursor protein fragments of various molecular size classes.

Journal of Endocrinology (1989) 123, 333–340
Ontogeny of pulsatile gonadotrophin secretion and pituitary responsiveness in male puberty in man: a mixed longitudinal and cross-sectional study
Authors: Wu F. C. W. , Borrow S. M. , Nicol K. , Elton R. , Hunter W. M.
Published: December 2008

The onset of puberty is characterized by a sleep-associated increase in pulsatile LH secretion which is not observed in adults. The ontogeny of gonadotrophin secretion during pubertal maturation may reflect changes in endogenous LHRH secretion, pituitary sensitivity to LHRH and/or alterations in gonadal steroid feedback. To understand the interplay between these mechanisms, we have examined the pulsatile pattern of plasma LH, FSH, testosterone, oestradiol and prolactin between 20.00 and 09.00 h and the pituitary response to repeated exogenous LHRH stimulation in 16 boys with delayed puberty (age 16·3±2·7 (s.e.m.) years) on one to four occasions in a mixed longitudinal/cross-sectional analysis. Physical maturity was determined by Tanner G staging (1–5) and clinical progress followed for a mean duration of 22·4 ± 8·5 months during which 33 hormone profiles were obtained.

Nocturnal (23.00–09.00 h) LH pulse frequency increased to a peak of 0·54±0·03/h at stage 2 which was followed by a gradual decline to 0·42 ± 0·04/h at stage 5. The appearance of LH pulses in the evening (20.00–23.00 h), probably representative of the rest of the day, was delayed until mid-puberty from which point frequency increased to a peak of 0·53 ±0·08/h at stage 5. LH pulse amplitude showed a linear increase from stages 1 to 5, with nocturnal pulse amplitudes being higher than evening pulses throughout. FSH did not show a clear pulsatile pattern. The LH: FSH ratio reversed from < 1 to > 1 at stage 2. The LH response to exogenous LHRH increased in parallel with LH pulse amplitude. There was no difference in the pattern of LH response to repeated LHRH stimulation as puberty advanced; the first stimulus always elicited a greater response than subsequent doses. In contrast, the FSH response to LHRH was maximal at stage 1 and became attenuated thereafter. The estimated mean nocturnal LHRH concentration or amplitude did not show any increase during pubertal maturation from 20·42±11·57 at stage 1 to 35·96 ± 20·83 ng/l at stage 5.

In conclusion, the sequential changes in this study suggest that the sleep-entrained increase in LHRH pulse frequency plays a key role at the onset of puberty. By enhancing pituitary responsiveness and setting in motion a cascade of events, this peripubertal augmentation of LHRH pulse frequency can account for most of the subsequent changes in LH, FSH and testosterone secretion during pubertal development in the male without any apparent alteration in LHRH pulse amplitude.

Journal of Endocrinology (1989) 123, 347–359
Diabetes mellitus and the sodium electrochemical gradient across the brush border membrane of rat intestinal enterocytes
Authors: Debnam E. S. , Ebrahim H. Y.
Published: December 2008

The effects of chronic diabetes mellitus of 4–5 weeks duration on the potential difference across the brush border membrane of rat small intestine (Vm) and on Na+-dependent uptake of d-glucose by jejunal brush border vesicles have been studied. Diabetes increased Vm in the jejunum from a mean value of −47.2 mV in control tissue to −57.4 mV in diabetic tissue (P<0.001) but was without effect on ileal Vm. Measurements of Vm during ion-substitution experiments revealed that the conductance of Na+ of the jejunal brush border was reduced by diabetes, whilst K+ and Cl− permeabilities were unaltered. Uptake studies using brush border vesicles and an Na+-electrochemical gradient showed that diabetes caused a 56% increase in the initial rate of uptake of d-glucose but was without effect on the peak to equilibrium ratio. Taken together, data from these two studies suggest that the lower Na+ permeability of the brush border in diabetes enhances the electrical and chemical driving force for active Na+-dependent uptake of glucose by reducing glucose-independent movement of Na+ across this membrane. Finally, the possible humoral factors involvedin this response to diabetes are discussed.

Journal of Endocrinology (1989) 123, 453–459
Follicle-stimulating hormones in anterior pituitary glands from children and adults differ in relation to sex and age
Authors: Wide L.
Published: December 2008

Follicle-stimulating hormone (FSH) in extracts of the anterior lobe of pituitaries, collected at autopsy from 13 boys, 21 girls, 17 men and 26 women, was measured in terms of biological activity (B) in vitro by the Sertoli cell aromatase bioassay, and in terms of immunological activity (I) by a radioimmunoassay.

The highest concentration of FSH in the anterior lobe found by bioassay was in young girls, who had a mean value three to seven times higher than that in young and elderly men and women and nine times higher than that in young boys. The total amount of FSH in the pituitary found by bioassay and immunoassay was very much less in young boys than in all other groups.

The B/I ratio of FSH was higher for all the 27 children below 10 years of age than for any of the 43 adults. This difference in B/I ratio of FSH in whole pituitary extracts persisted in fractions after electrophoretic separation. The mean B/I ratio for young girls was 1·26 times higher than that for young boys and 2·25 times higher than that for adults. Young and elderly men and women had almost identical B/I ratios.

All extracts were analysed after electrophoresis and the median charge and charge homogeneity of FSH were estimated. The number of different forms of FSH in pituitary extracts from a child was at least 20–30, similar to that in an adult. In girls, the median charge of FSH was similar to that of young women and significantly less negative than in elderly women. The median charge of FSH in boys was more negative than in girls, but less negative than in both young and elderly men.

After treatment of pituitary extracts with neuraminidase, the median charge of FSH in infants was significantly more negative than that in adults. This, together with the differences in B/I ratios between children and adults, indicates a change at puberty in the molecular structure of FSH from juvenile to adult forms of the hormone.

Journal of Endocrinology (1989) 123, 519–529
CONJUGATES OF OVARIAN STEROIDS, INCLUDING 17α, 20β-DIHYDROXY-4-PREGNEN-3-ONE (MATURATION-INDUCING STEROID), ACCUMULATE IN THE URINE OF A MARINE TELEOST (PLAICE; PLEURONECTES PLATESSA)
Authors: Canario Adelino V. M. , Scott A. P.
Published: December 2008

Free and conjugated 17α, 20β-dihydroxy-4-pregnen-3-one (17, 20β-P), 17α, 21-dihydroxy-4-pregnene-3, 20-dione (11-deoxycortisol) and 3α, 17α, 21-trihydroxy-5β-pregnan-20-one (3α, 17, 21-P-5β) were measured by radioimmunoassay in matching blood plasma and urine samples from plaice (Pleuronectes platessa) females at several ovarian maturity stages: post-vitellogenesis (IV), final oocyte maturation (V), and ovulation (VI).

Free steroids were generally low in all samples. Conjugated steroids were up to 2 orders of magnitude higher in urine than in plasma samples. Conjugated 17, 20β-P was higher in stage V than in stage IV or VI females. Conjugated 11-deoxycortisol was higher in stage IV and V females. Conjugated 3α, 17, 21-P-5β was higher in stage V and VI females.

These results support earlier studies which indicated that 17, 20β-P was the most likely maturation-inducing steroid (MIS) in plaice, and that the urine might be a vehicle for steroid pheromones synthesized by the gonads.
INSULIN AND VARIATION IN GLUCOSE LEVELS MODIFY THE SECRETION RATES OF THE GROWTH HORMONE-INDEPENDENT INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-1 IN THE HUMAN HEPATOBLASTOMA CELL LINE HEP G2
Authors: Cotterill A.M. , Cowell C.T. , Silink M.
Published: December 2008

The plasma level of the GH-independent insulin-like growth factor binding-protein-1 (IGFBP-1) is regulated inversely by insulin. In this study the effect of insulin and changes in the glucose concentration on in-vitro IGFBP-1 secretion by the Hep G2 cell line was studied. Media from confluent cells in 12 replicates were collected for consecutive periods: initial control (20 h), study(6 h) and recovery (20 h). Insulin suppressed IGFBP-1 secretion maximally at 100 mU/1 (−32%) within 6 h. The secretion of IGFBP-1 was stimulated by a decrease in the glucose concentration in the medium, maximally (+25%) with a decrease from 24 to 6 mmol/l. Stimulation by varying glucose levels and suppression by insulin of IGFBP-1 secretion persisted on return to control conditions after the removal of physiological concentrations of glucose (4 - 12 mmol/l) and insulin (50 - 500 mU/1). The findings in the Hep G2 cell line that a variation in the physiological concentrations of glucose and insulin each independently regulate IGFBP-1 secretion suggest that this cell line may by a suitable model for further in-vitro studies of the regulation of secretion of IGFBP-1.
Iodide autoregulation of functional and morphological differentiation events in the FRTL-5 rat thyroid cell strain
Authors: Beere H. M. , Tomlinson S. , Bidey S. P.
Published: December 2008

The role of cyclic AMP (cAMP) attenuation in mediating the autoregulatory actions of iodide on thyroid cell iodide uptake and surface morphological responses to TSH was investigated in the rat thyroid cell strain FRTL-5. Preincubation of cells for 6 h with up to 1 mmol sodium iodide/1 led to a progressive reduction in both accumulation of cAMP and iodide uptake responses to TSH. Forskolin-mediated accumulation of cAMP and iodide uptake responses were similarly reduced after preincubation with iodide, whilst the iodide accumulation response to dibutyryl cAMP (dbcAMP) was unaffected. The inhibitory effects of iodide on TSH or forskolin-responsive iodide accumulation were not seen if preincubation was limited to 3 h, and were also abolished by the thionamide drug methimazole (1 mmol/l). Medium containing 1 μmol iodide/l prevented the appearance of the surface microvilli and pseudopodia normally observed after re-addition of TSH or forskolin, although cytoplasmic retraction was still apparent under such conditions. In contrast, iodide was without effect on the ability of dbcAMP (1 mmol/l) to induce cytoplasmic retraction and the formation of microvilli and pseudopodia. Inclusion of 1 mmol sodium perchlorate/l together with iodide during preincubation failed to prevent or reduce the suppression by iodide of either iodide uptake or surface morphological differentiation, suggesting that both aspects of autoregulation may involve surface actions of organified iodide. These observations indicate that in FRTL-5 cells, autoregulation by iodide of both the functional and surface morphological actions of TSH principally reflects the attenuating activities of organified iodide on intracellular cAMP generation.

Journal of Endocrinology (1990) 124, 19–25
Differential effects of a unilateral hypothalamic lesion on ovulation and compensatory ovarian hypertrophy in hemiovariectomized adult rats
Authors: Cruz M. E. , Moran J. L. , Jaramillo L. P. , Domínguez R.
Published: December 2008

The effects were analysed of a unilateral lesion in the anterior or medial hypothalamus made on the day of oestrus on right or left hemicastrated rats. On the day of oestrus after two consecutive oestrous cycles of the same length, the ovulation rate in rats with lesions in the anterior left hypothalamus was lower than in control hemicastrated animals (5/16 vs 18/20; P<0·01), and normal in those rats with lesions in the right side (14/18). None of the animals with lesions in the left side of the anterior hypothalamus and with the left ovary in situ ovulated (0/7), but 5/9 with the right ovary in situ did ovulate (P<0·05). Lesions on either side of the medial hypothalamus did not modify ovulation rate. Compensatory ovulation was reduced in those animals with lesions in the right anterior hypothalamus and with the right ovary in situ. Lesions in either side of the medial hypothalamus reduced compensatory ovulation. Lesions in the right side of the anterior and medial hypothalamus increased compensatory ovarian hypertrophy in the left ovary and decreased it in the right ovary. Lesions in the left side of the anterior hypothalamus increased compensatory ovarian hypertrophy in the left ovary only, whereas lesions in the left side of the medial hypothalamus reduced compensatory ovarian hypertrophy in the right ovary. The results suggest that the information arising in each side of the anterior and medial hypothalamus plays different roles in the ipsi-and contralateral ovary, when either the left or the right ovary is absent.

Journal of Endocrinology (1990) 124, 37–41
Differential ovulatory responses of the right and left ovaries of the adult rat to unilateral lesion and anaesthesia of the cervico-vaginal plexus
Authors: Domínguez R.
Published: December 2008

Differences were observed in the ovulation rates of the right and left ovaries in response to unilateral lesions of the cervico-vaginal plexus (CVP) followed by pseudopregnancy or by anaesthesia of the CVP induced with panthocaine plus adrenaline (right ovary 6·7±0·4 (s.e.m.) vs left ovary 4·6 ± 0·9; P<0·05). Pseudopregnancy (days showing a dioestrous smear after copulation with a vasectomized male before an oestrous smear following a pro-oestrous one) lasted longer in rats with a lesion in the CVP than in a control pseudopregnant group (14·9 ± 0·5 vs 11·2 ± 0·5; P < 0·01). Anaesthesia of the CVP performed on each day of the oestrous cycle did not modify the ovulation rate compared with laparotomized animals. Both laparotomy and anaesthesia of the CVP performed on oestrus or day 1 of dioestrus blocked ovulation but when they were performed on day 2 of dioestrus or pro-oestrus they failed to do so (laparotomy 9/18 vs 12/14, P<0·05; anaesthesia of CVP 3/11 vs 17/17, P < 0·05). The number of ova shed by the left ovary in animals with anaesthetized CVP was lower than by the right ovary (4·5 ± 0·6 vs 6·2 ± 0·5; P<0·05). These results add further support to the idea that the CVP participates in the regulation of ovulation rate, and that the left ovary is less adaptable than the right when innervation is challenged.

Journal of Endocrinology (1990) 124, 43–45