bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytochromes P-45011β, P-450scc and adrenodoxin gene expression during adrenocortical regeneration in the rat
Authors: Chou F.-P. , Gallant S. , Brownie A. C.
Published: December 2008

Circulating levels of 11-deoxycorticosterone are increased during the development of adrenal-regeneration hypertension. The present studies were undertaken to examine the mechanisms involved in this increase. Plasmids containing cDNA inserts coding for cytochrome P-45011β, cytochrome P-450scc and adrenodoxin were used to determine, by Northern blot analysis, mRNA levels at 1, 2 and 3 weeks of adrenal regeneration. There was a striking decrease in mRNA transcripts for all three enzymes during the first week of regeneration when compared with intact adrenal tissue. Over the next 2 weeks the mRNA levels increased to 64% for P-450 11β, to 80% for P-450scc and to 82% for adrenodoxin. Actin mRNA levels were 70% of control levels in the first week but were back to control levels by the second week. The present findings suggest that decreased expression of steroid 11β-hydroxylase could contribute to the increased secretion of 11-deoxycorticosterone during the early stages of adrenal regeneration.

Journal of Endocrinology (1989) 122, 403–408
Increased levels of a humoral digitalis-like factor in deoxycorticosterone acetate-induced hypertension in the pig
Authors: Hamlyn J. M.
Published: December 2008

Plasma levels of an endogenous digitalis-like factor (EDLF) and atrial peptides were followed in pigs confined to metabolic cages during the development of deoxycorticosterone acetate (DOCA)-induced hypertension. During the first 2 days of DOCA treatment, urinary sodium excretion decreased and the plasma levels of renin and atrial peptide fell significantly. During this period, plasma levels of EDLF increased > 30-fold from a baseline of <0·25 to 9·72 nmol ouabain equivalents/l. Between days 2 and 5 of DOCA treatment, urinary sodium returned to preDOCA levels ('mineralocorticoid escape') and during this period significant increases of atrial peptide and mean arterial pressure (MAP) and a decrease in EDLF were found. Following mineralocorticoid escape there was a secondary rise in levels of EDLF and atrial peptide and both phenomena correlated with MAP (EDLF, r = 0·87, P< 0·05; atrial peptide, r = 0·9, P< 0·05) and with each other (r = 0·96, P < 0·05) over a 20-day period. Acute expansion of extracellular fluid volume before DOCA elicited significant increments in plasma EDLF and atrial peptide. Volume loading during chronic DOCA treatment increased plasma EDLF significantly whereas no response of atrial peptide was detected. These results suggest that DOCA affects the reactivity of mechanisms involved in the perception of and/or response to acute changes in volume status. However, neither EDLF nor atrial peptide appear to be viable candidates as direct mediators of mineralocorticoid escape. Finally, the nature of the changes found in EDLF and atrial peptide levels during DOCA treatment suggest that these factors are involved in the long-term control of blood pressure in this model of low renin hypertension.

Journal of Endocrinology (1989) 122, 409–420
Adaptive responses to sustained volume expansion in hyponatraemic rats
Authors: Verbalis J. G. , Drutarosky M. D. , Ertel R. J. , Vollmer R. R.
Published: December 2008

Studies were carried out to evaluate adaptive responses to water retention in an experimental model of the syndrome of inappropriate antidiuresis (SIAD). Hyponatraemia was induced by continuous s.c. infusions of the antidiuretic vasopressin analogue 1-deamino-[8-d-arginine]-vasopressin in rats ingesting a 5% (w/v) dextrose solution. After 48 h of sustained decreases in the plasma concentration of Na+ to 23–25% of normal levels, all body fluid compartments were significantly expanded: plasma volume estimated by changes in plasma protein concentration was increased by 26%, extracellular fluid volume estimated by 22Na volume of distribution was increased by 24%, and total body water estimated by 3H2O volume of distribution was increased by 16%. Despite marked increases in all body fluid compartment volumes, mean arterial blood pressure was only modestly increased to 110 ± 2 mmHg in conscious hyponatraemic rats. Consistent with the sustained volume expansion, both basal and stimulated plasma renin activities were significantly suppressed in the hyponatraemic rats. Plasma vasopressin levels were similarly suppressed, and the hyponatraemic rats showed a striking absence of endogenous vasopressin secretion in response to marked intravascular volume depletion (15–45%) produced by s.c. administration of polyethylene glycol. Plasma concentrations of atrial natriuretic peptide were initially stimulated four- to fivefold above basal levels in response to the water-induced volume expansion, but by 48 h fell to ranges not significantly different from basal unstimulated levels, despite continued plasma and extracellular fluid volume expansion at that time.

These results illustrate that multiple haemodynamic and hormonal adaptive responses occur with sustained dilutional hyponatraemia in rats, and suggests that these can be of sufficient magnitude to allow continued water retention without necessarily provoking either escape from antidiuresis or continued natriuresis. In contrast with previous studies in experimental animals in which hyponatraemia was maintained by continuous forced administration of hypotonic fluid, rats in this model reached a steady state with characteristics resembling many of those observed clinically in patients with SIAD.

Journal of Endocrinology (1989) 122, 421–431
Growth hormone acutely increases glucose output by hepatocytes isolated from hypophysectomized rats
Authors: Blake W. L. , Clarke S. D.
Published: December 2008

A series of experiments using isolated rat hepatocytes was carried out to establish rat liver cells in suspension as a physiological model for examining GH responses, and to determine whether acute recombinant bovine GH (rbGH) treatment of rat liver cells increased glucose output and/or suppressed fatty acid synthesis from lactate. Rat liver cells were isolated by collagenase perfusion and incubated in short-term (<60 min) suspension. The amount of insulin, glucagon or vasopressin required to elicit a half-maximal response was within the physiological range of the circulating hormone. When hepatocytes from normal rats were acutely (<60 min) treated with 0, 0·1, 10, 100 or 1000 nmol rbGH/l, rates of hepatocyte glucose output and fatty acid synthesis were unaltered. In addition, acute rbGH treatment (1000 nmol/l) did not alter hepatocyte responsiveness to insulin or vasopressin. However, acute rbGH treatment of hepatocytes isolated from hypophysectomized rats significantly (P < 0·05) increased the rate of glucose output twofold and moderately (P<0·10) enhanced fatty acid synthesis. The accelerated rate of glucose production was not accompanied by an increase in the amount of glycogen phosphorylase-a. The observations with liver cells from hypophysectomized rats are not consistent with a GH receptor-transducing mechanism which is like that for glucagon (adenylate cyclase-linked) or insulin (tyrosine kinase-linked).

Journal of Endocrinology (1989) 122, 457–464
Radioimmunoassay of inhibin in the serum of male monkeys
Authors: Fingscheidt U. , Weinbauer G. F. , Robertson D. M. , de Kretser D. M. , Nieschlag E.
Published: December 2008

A heterologous inhibin radioimmunoassay method to measure inhibin in serum of male cynomolgus (Macaca fascicularis) and rhesus (Macaca mulatta) monkeys has been validated using a specific antibody against bovine 31 kDa inhibin and 125I-labelled 31 kDa inhibin as tracer. A serum pool from male monkeys was used as standard. Serial dilutions of normal monkey serum showed parallel logit–log dose–response curves to purified porcine and bovine inhibin as well as to a female human serum pool. The intra-assay coefficient of variation was 4·2% (n=10) and the interassay coefficient of variation 5·1% (n=10). No loss of inhibin immunoactivity was noted after storage at 23 °C for 5 days or repeated thawing and freezing of the serum samples. Serum from castrated monkeys showed undetectable levels of inhibin. Treatment with a gonadotrophin-releasing hormone agonist for 15 weeks led to a marked suppression of peripheral serum inhibin to concentrations similar to those after hypophysectomy or pituitary stalk section.

Journal of Endocrinology (1989) 122, 477–483
Testes are asymmetric in the testicular hemicastration response of the male rat
Authors: Frankel A. I. , Chapman J. C. , Cook B.
Published: December 2008

An enquiry was made into variability in the testicular hemicastration response of the mature rat (doubling of testicular vein testosterone concentration from the remaining testis 24 h after hemicastration). The response was shown to be asymmetric, being more reliable and more robust when the left testis was removed first. Apparently the testicular hemicastration response, which has been shown to be neurally controlled, shares the asymmetry which has been reported recently in the neural regulation of unilateral ovariectomy.

Journal of Endocrinology (1989) 122, 485–488
Suppression and recovery of pituitary gonadotrophin secretion in intact and orchidectomized rats treated neonatally with a gonadotrophin-releasing hormone antagonist
Authors: Kolho K.-L. , Huhtaniemi I.
Published: December 2008

Suppression of neonatal rat pituitary-testis function by gonadotrophin-releasing hormone (GnRH) antagonists results in delayed sexual maturation and infertility. Since the mechanism is not understood, the acute effects of a GnRH antagonist on gonadotrophin secretion in neonatal male rats has been studied in more detail. Treatment with a GnRH antagonist analogue, N-Ac-d-Nal(2)1,d-p-Cl-Phe2,d-Trp3,d-hArg(ET2)6,d-Ala10-GnRH (2 mg/kg per day) on days 1–10 of life had prolonged effects on gonadotrophin secretion; serum LH and FSH recovered in 1 week, but the pituitary content took 2 weeks to recover. Likewise, LH and FSH responses to acute in-vivo stimulation with a GnRH agonist were still suppressed 1 week after the treatment. Interestingly, a rebound (86% increase) in basal serum FSH was found 16 days after treatment with the antagonist.

Whether testis factors influence gonadotrophin secretion during treatment with the GnRH antagonist and/or in the subsequent recovery period was also assessed. Neonatal rats were castrated on days 1, 5 or 10 of the 10-day period of antagonist treatment. Orchidectomy on days 1 and 5 only marginally affected gonadotrophin secretion. When orchidectomy was performed at the beginning of the recovery period, no effects on pituitary recovery were seen within 1 week of castration. After 16 days, serum LH and FSH in the antagonist-treated and control castrated rats were equally increased but the pituitary contents of the antagonist-treated rats were still suppressed.

Finally, the effect of testosterone treatment on the recovery of gonadotrophin secretion after antagonist suppression was studied in intact and orchidectomized animals. The rats were implanted with testosterone capsules for 7 days after treatment with the GnRH antagonist in the neonatal period. Testosterone suppressed pituitary LH contents similarly in all groups of animals, but had no effects on serum LH. Paradoxically, serum FSH was suppressed 50% by testosterone in intact and castrated antagonist-treated rats and in castrated controls but not in intact controls. These findings suggest that suppression of FSH by testosterone is only seen in neonatal animals with low endogenous levels of this androgen, whether due to GnRH antagonist treatment or castration.

It is concluded that neonatal treatment with a GnRH antagonist results in prolonged suppression of LH and FSH secretion, that testis factors play only a minor role in pituitary modulation during the antagonist suppression and that more disturbances are observed in the post-treatment recovery of FSH secretion than in that of LH.

Journal of Endocrinology (1989) 122, 519–526
Stimulatory effect of caffeine on the hypothalamo-pituitary-adrenocortical axis in the rat
Authors: Nicholson S. A.
Published: December 2008

Intraperitoneal injection of caffeine (12·5–100 mg/kg) into rats caused a significant, dose-related increase in plasma corticosterone 2 h later, when the greatest response was measured. The corticosterone response to laparotomy stress or i.v. injection of ACTH(1–24) was unaffected by prior injection of caffeine. The response to stress or caffeine was unaffected by adrenal enucleation 28 days previously.

In vitro, 10 mmol caffeine/l stimulated basal release of corticosterone from adrenal quarters and potentiated the response to a sub-maximal stimulatory concentration of cyclic AMP (cAMP). The drug had no effect on release stimulated by a sub-maximal concentration of ACTH(1–24).

Release of ACTH from pituitary fragments incubated in vitro was stimulated in a dose-related manner by caffeine (0·01–10 mmol/l), and the responses to hypothalamic extract and sub-maximal concentrations of corticotrophin-releasing factor (CRF-41) or arginine vasopressin (AVP), but not cAMP, were significantly enhanced by 10 mmol caffeine/l.

Release of immunoreactive CRF-41 (but not AVP) was significantly increased by caffeine (0·01–10 mmol/l) added to hypothalami incubated in vitro. The response to injection of caffeine in vivo was completely prevented by pharmacological blockade of endogenous CRF release.

Taken together, these results show that caffeine at high concentrations can stimulate directly the release of the hormones of the hypothalamo-pituitary-adrenocortical axis in vitro, but the fact that these concentrations are unlikely to be reached after administration in vivo suggests that the effect of caffeine may be mediated centrally.

Journal of Endocrinology (1989) 122, 535–543
Melatonin specifically stimulates type-II thyroxine 5′-deiodination in brown adipose tissue of Syrian hamsters
Authors: Puig-Domingo M. , Guerrero J. M. , Menéndez-Pelaez A. , Reiter R. J.
Published: December 2008

The response of type-II thyroxine 5′-deiodinase (5′-DII)DII) to melatonin treatment was studied in the Syrian hamster. Male hamsters were treated for 15 days with a s.c. pellet containing melatonin, and 5′-DII activity in brown adipose tissue, anterior pituitary gland, Harderian gland and pineal gland was measured using a radioenzymatic technique. Melatonin-treated animals exhibited enhanced 5′-DII activity restricted to brown adipose tissue; the increase was threefold above the values measured in the control group. Serum concentrations of thyroid hormones were unaffected by melatonin treatment. We conclude that the stimulatory effect of melatonin on type-II thyroxine 5′-deiodination is specifically directed to the isoenzyme located in brown adipose tissue and is not accompanied by changes in serum thyroid hormones.

Journal of Endocrinology (1989) 122, 553–556
Protein metabolism in ovine primary muscle cultures derived from satellite cells – effects of selected peptide hormones and growth factors
Authors: Roe J. A. , Harper J. M. M. , Buttery P. J.
Published: December 2008

Methods were developed for the isolation and culture of satellite cells from adult sheep muscle. Differentiated cultures of these cells were used to investigate the effects of four hormones and growth factors on protein synthesis and degradation. Insulin was found to have no effect except at supraphysiological concentrations (100 nmol/l and 1 μmol/l) where it is probably cross-reacting with the insulin-like growth factor (IGF) type-I receptor. IGF-I was found to be anabolic at lower concentrations (1–3 nmol/l). Epidermal growth factor (EGF) had a smaller effect on protein synthesis and degradation than insulin or IGF-I. The specific activity of the muscle-specific enzyme creatine phosphokinase (CPK) was increased by treatment with EGF. When both IGF-I and EGF were present in the test media an additive effect on protein synthesis was observed. However, no additive effect of IGF-I and insulin was noted. No effects of bovine GH were seen.

Journal of Endocrinology (1989) 122, 565–571
Aromatase, 5α- and 5β-reductase in brain, pituitary and skin of the sex-role reversed Wilson's phalarope
Authors: Schlinger B. A. , Fivizzani A. J. , Callard G. V.
Published: December 2008

While intrasexual competition for mates is generally considered to be an androgen-dependent characteristic of reproductively active males, in the Wilson's phalarope (Phalaropus tricolor) it is the female that acquires the brighter nuptial plumage and aggressively competes for access to the less aggressive males. Despite this pronounced sex-role reversal, circulating sex steroid hormones of breeding phalaropes are similar to those of avian species displaying traditional male–female reproductive roles. To investigate whether these behavioural and morphological steroid-dependent differences may be due to differences in target organ metabolism of circulating androgen, [3H]androstenedione in the presence of an NADPH-generating system was incubated with homogenates of brain, pituitary and skin of male and female Wilson's phalaropes collected from a naturally breeding population. Oestrone, 5α-androstanedione and 5β-androstanedione were measured as endpoints of aromatization, 5α-reduction and 5β-reduction respectively. Aromatase activity in the anterior hypothalamus/preoptic area (AHPOA) and posterior hypothalamus was greater in breeding males with high circulating concentrations of testosterone than in females, and activity in the AHPOA was greater in breeding than in non-breeding males (with low circulating testosterone). Aromatase levels did not differ in septum, archistriatum, hyperstriatum or pituitary. 5α- and 5β-reductase were detected in all neuroendocrine tissues sampled and although there were no significant male–female differences, 5α-reductase was greater in the AHPOA of breeding than of non-breeding males. We infer from this that the behavioural sex-role reversal of phalaropes is unlikely to be accounted for by differences in androgen metabolism in neural targets, although the capacity to form greater quantities of oestrogenic and 5α-reduced metabolites in the AHPOA of breeding males may be linked to the expression of masculine copulatory behaviours. Aromatase activity was not detected in skin containing a sexually dimorphic feather tract; however, 5α- and 5β-reductase activities were significantly higher in females than in males and may account for the brighter nuptial plumage of females. These data suggest that alternate determinants of neural responsiveness such as sex-steroid receptor abundance or neural circuitry may underlie atypical sexual behaviours in phalaropes.

Journal of Endocrinology (1989) 122, 573–581
Effects of infusions of various doses of bovine growth hormone-releasing factor on blood hormones and metabolites in lactating Holstein cows
Authors: Enright W. J. , Chapin L. T. , Moseley W. M. , Zinn S. A. , Kamdar M. B. , Krabill L. F. , Tucker H. A.
Published: December 2008

In two experiments, the effects of i.v. infusions of various doses of bovine GH-releasing factor (GRF) on blood hormones and metabolites in lactating Holstein cows were determined.

In experiment 1, cows were infused with GRF (0, 3·125, 6·25, 12·5, 25·0 or 50·0 mg/cow per 24 h) for 24 h. Blood was sampled at −1, 5, 11, 15 and 23 h relative to the start of the infusion. The serum concentration of somatomedin C (SM-C) before infusion was 303 ± 8 (s.e.m.) μg/l. Doses of GRF of between 3·125 and 50·0 mg were equipotent in stimulating (P < 0·05) SM-C by 1·5- to 2·5-fold. GRF-induced increases in SM-C occurred by 11 h from the start of the infusion.

In experiment 2, primiparous cows were infused with GRF (0, 1 or 3 mg/24 h) for 20 days. Blood was sampled for 12 h on days 1, 10 and 19. The 1 mg dose of GRF increased (P < 0·05) blood concentrations of SM-C (on days 10 and 19) and glucose (on day 19), but did not affect blood concentrations of prolactin, insulin, cortisol, tri-iodothyronine (T3), thyroxine (T4), non-esterified fatty acids (NEFA) or glucose. The 3 mg dose of GRF increased (P < 0·05) blood concentrations of SM-C (on days 10 and 19), T3 (on days 10 and 19), insulin (on day 19), NEFA (on days 1, 10 and 19) and glucose (on day 19), but did not affect blood concentrations of prolactin, cortisol or T4.

We conclude that these data are consistent with the hypothesis that the galactopoietic effect of exogenous GRF in dairy cattle is mediated by increased secretion of GH.

Journal of Endocrinology (1989) 122, 671–679
Effect of acetylcholine and 5-hydroxytryptamine on the secretion of corticotrophin-releasing factor-41 and arginine vasopressin from the rat hypothalamus in vitro
Authors: Hillhouse E. W. , Milton N. G. N.
Published: December 2008

Previous studies using the isolated rat hypothalamus in vitro have shown that both acetylcholine and 5-hydroxytryptamine (5-HT) stimulate the secretion of bioactive corticotrophin-releasing factor (CRF). However, the CRF complex consists of a number of bioactive substances, and in this study we examined the effect of acetylcholine and 5-HT on the release of immunoreactive (ir)-CRF-41 and ir-arginine vasopressin (AVP) in vitro. Acetylcholine caused a dose-dependent (10 pmol–10 nmol/l) release of both neuropeptides, and the effect was partially antagonized by both atropine and hexamethonium. Nicotine (0·1–10 μmol/l) also stimulated the release of both peptides, whereas bethanacol had no effect on AVP release, but had a variable action on CRF-41 release. 5-HT caused a dose-dependent (10 pmol–1 nmol/l) stimulation of CRF-41 release without any effect on AVP release, and this effect was antagonized by cyproheptadine, suggesting the participation of specific 5-HT receptors.

Journal of Endocrinology (1989) 122, 713–718
A comparison of the seasonal hormone changes and patterns of growth, voluntary food intake and reproduction in juvenile and adult red deer (Cervus elaphus) and Père David's deer (Elaphurus davidianus) hinds
Authors: Loudon A. S. I. , Milne J. A. , Curlewis J. D. , McNeilly A. S.
Published: December 2008

Non-domesticated seasonally breeding ungulates exhibit marked seasonal changes in metabolic rate, voluntary food intake (VFI), pelage growth and moult and hormone secretion. It is not known whether these seasonal rhythms are regulated by the same central processes which control the onset and termination of the breeding season. Here we compare two closely related deer species which have significantly different mating and calving seasons. Seasonal changes in VFI, liveweight, coat growth, plasma prolactin and tri-iodothyronine (T3), and the timing of the breeding season were examined over a 15-month period in six adult post-pubertal red and Père David's deer from January to April the following year. The timing of the seasonal changes in prolactin, T3, VFI and coat growth were all significantly advanced by 56, 23, 60 and 54 days respectively in the Père David's deer. The times of onset and termination of the breeding season of Père David's deer were also significantly advanced by 90 days, but in both species, the breeding season was of similar duration (160 ± 5 (s.e.m.) days). Changes in liveweight of adult red deer could be explained by changes in VFI rather than efficiency of utilization. This was not the case in Père David's deer and may indicate seasonal changes in the efficiency of energy utilization. In order to establish whether these species differences develop with age, we undertook a second study in which seasonal changes in VFI, growth, plasma prolactin concentrations and the timing of the onset of the breeding season were recorded for ten red deer and six Père David's deer from 6 to 18 months of age. Both species exhibited a similar decline in VFI in the first autumn of life. Subsequently, the Père David's deer exhibited an advance in the timing of the seasonal peak in VFI and prolactin (21 and 66 days respectively); puberty occurred 3 months earlier than in red deer. The earlier breeding season of the Père David's deer was associated with a significant advance in a range of seasonal endocrine and physiological parameters. These species differences may develop with age. Our data indicate that seasonal patterns of metabolism and growth may be closely linked to those mechanisms which also regulate the onset and termination of the breeding season.

Journal of Endocrinology (1989) 122, 733–745
Quantification of opioid-binding sites in the ewe hypothalamus
Authors: Yang K.-P. , Haynes N. B. , Lamming G. E.
Published: December 2008

Opioid-binding sites were quantified in the ewe hypothalamus using [3H]diprenorphine ([3H]DIP) as the radioligand. [3H]DIP binding to hypothalamic membrane preparations was stereospecific, saturable with respect to [3H]DIP concentration, and linear with hypothalamic membrane protein content. Scatchard analysis revealed a single class of binding sites. There were no significant differences in binding site concentration or binding affinity in hypothalami from intact ewes during the breeding and non-breeding seasons, or from long-term ovariectomized ewes with and without oestradiol treatment during the breeding season. Thus, whilst ovarian steroid hormones are known to modify LH responses to opioids and their antagonists in the ewe in vivo, they do not appear to do this by modulating the numbers of hypothalamic opioid-binding sites.

Journal of Endocrinology (1989) 122, 763–767
AMPLIFICATION OF UTEROGLOBIN SECRETION BY ALTERNATING PROLACTIN-PROGESTERONE ADMINISTRATION
Authors: Daniel J. C. , June ja S. C.
Published: December 2008

Long-term ovariectomized rabbits were given injections of progesterone and prolactin in an alternating sequence (progesterone for 5 days, prolactin for 4 days and progesterone for 5 days) to test the hypothesis that each of these hormones acts to increase the other's receptor, resulting in a positive feedback process whereby prolactin augments the progesterone-dependent increase in the mRNA for the uterine protein, uteroglobin. The results of this study support the hypothesis, in that the experimental rabbits produced exceptionally large concentrations of uteroglobin.
Comparison of the effects of administration of recombinant bovine growth hormone or N-Met insulin-like growth factor-I to lactating goats
Authors: Davis S. R. , Gluckman P. D. , Hodgkinson S. C. , Farr V. C. , Breier B. H. , Burleigh B. D.
Published: December 2008

Five goats were injected with GH (15 mg/day), three goats received systemic infusions of insulin-like growth factor (IGF)-I (43 nmol/h) and four goats received systemic infusions of physiological saline (20 ml/h) on days 4–6 of a 10-day experimental period during mid-lactation.

Milk yield increased by an average of 24% in GH-treated goats by the time of the third injection. In contrast, milk yield of IGF-I-infused goats did not differ from saline-infused animals although two of three goats did show a small increase (12%) after 36 h of IGF-I infusion.

With GH and IGF-I treatments plasma IGF-I concentrations increased similarly, reaching maxima of 100–130 nmol/l within 24 h. Plasma IGF-I concentration was relatively constant in saline-infused goats at about 50 nmol/l throughout the experiment.

Total IGF-I bound to 50 kDa and 150 kDa binding proteins in plasma was increased by GH and IGF-I treatments but, in contrast to IGF-I, GH increased the proportion of IGF-I bound to 150 kDa binding protein.

In a second experiment, four goats received systemic infusion of IGF-I (43 nmol/h) and four goats received systemic infusion of physiological saline (20 ml/h). There was no evidence that milk yield was changed during IGF-I infusion. However, when those goats which had previously received IGF-I infusions were injected with GH, milk yield increased by 30%. While the increment in plasma IGF-I concentration during IGF-I infusion was similar to that obtained in the first experiment, the IGF-I response to GH injection was much greater, plasma concentrations rising to 230 nmol/l.

The data show a lack of milk yield response in goats whose plasma IGF-I concentrations were increased by IGF-I administration. Systemic infusion of IGF-I appears to be ineffective as a means of procuring a sustained increase in milk production.

Journal of Endocrinology (1989) 123, 33–39
Regulation by oestradiol of serum levels of LH and FSH and pituitary levels of gonadotrophin-releasing hormone receptors after ovariectomy in the rat
Authors: Rosen H. , Jameel M. L. , Dee C. , Barkan A. L.
Published: December 2008

We studied cyclic and ovariectomized, oestradiol-treated rats to investigate whether oestradiol concentrations before ovariectomy determine the dynamics of the rises in serum levels of LH and FSH, and in pituitary gonadotrophin-releasing hormone (GnRH) receptors after ovariectomy. In cyclic rats, ovariectomy on metoestrus (oestradiol = 44 pmol/l), but not at midnight of dioestrus (oestradiol =254 pmol/l) was followed by a rise in GnRH receptors 40 h later. Randomly cyclic females were ovariectomized under ether anaesthesia and treated with s.c. oestradiol implants for 2 days to provide serum levels spanning the physiological range. Exposure to lower oestradiol concentrations (48 or 74 pmol/l) resulted in significant rises in levels of LH and FSH, and in GnRH receptors earlier than exposure to higher (148 or 309 pmol/l) oestradiol levels (2 compared with 4 days). GnRH given for 24 h after removal of the implant was unable to induce a rise in GnRH receptors in any group, while LH and FSH responses to GnRH were proportional to the pretreatment levels of oestradiol. This suggests that the concentration of oestradiol before ovariectomy determines the subsequent dynamics of LH and FSH and of GnRH receptors through actions at the hypothalamic and pituitary level.

Journal of Endocrinology (1989) 123, 249–256
Relationship between insulin-like growth factor-I and low-density lipoprotein cholesterol levels in primary hypothyroidism in women
Authors: Hoogerbrugge–v.d.Linden N. , Jansen H. , Hülsmann W. C. , Birkenhäger J. C.
Published: December 2008

The effect of insulin-like growth factor-I (IGF-I) on the disturbance of lipid metabolism during primary hypothyroidism was studied in 12 women with primary hypothyroidism. Significant increases in both low-density lipoprotein (LDL) cholesterol and intermediate-density lipoprotein cholesterol were seen. Lipoprotein concentrations reverted to normal after substitution with thyroxine (T4) until the euthyroid state was reached. A decrease in IGF-I of 65% (P<0·005) was seen in hypothyroid patients and this was inversely correlated (r=−0·75; P<0·01) with the concentration of LDL cholesterol. Multivariate regression analysis of LDL cholesterol against IGF-I and free T4 showed that IGF-I determines the concentration of LDL cholesterol instead of free T4.

Our data suggest that in hypothyroidism, IGF-I is a determinant of the concentration of LDL cholesterol. In addition, hypothyroidism can influence plasma lipoprotein metabolism by lowering the activity of the salt-resistant lipase (liver lipase).

Journal of Endocrinology (1989) 123, 341–345
Biphasic response in the secretion of gonadotrophin-releasing hormone in ovariectomized ewes injected with oestradiol
Authors: Caraty A. , Locatelli A. , Martin G. B.
Published: December 2008

In ovariectomized ewes, an injection of oestrogen initially inhibits the tonic secretion of LH, and then induces a large release of LH similar to the preovulatory surge in intact ewes. The pattern of hypothalamic secretion of gonadotrophin-releasing hormone (GnRH) into the pituitary portal blood during this biphasic response to oestrogen was investigated in conscious, unrestrained, ovariectomized adult Ile-de-France ewes during the breeding season. The ewes were ovariectomized and implanted with cannulae for portal blood collection on the same day. Seven days later, portal and peripheral blood samples were collected simultaneously every 5 min for 25 h. The ewes were injected with oestradiol-17β (25 μg i.v. and 25 μg i.m.) 6·25 h after the start of sampling. GnRH and LH were measured by radioimmunoassay in portal and jugular plasma samples respectively.

A clear pulsatile pattern of LH secretion was observed before the oestradiol injection in all ewes, followed by the typical biphasic decrease (negative feedback) and increase (positive feedback) in mean concentrations. The sampling period was divided, for analysis, into pretreatment, negative feedback and positive feedback phases. Before injection with oestradiol, the GnRH pulses were clearly defined in portal blood and always synchronized with LH pulses in the peripheral circulation. The frequency was 5·9 ± 0·6 pulses/6 h (mean ± s.e.m.), and the amplitude was 31·6±7·6 pmol/l. During negative feedback, both the frequency (4·2 ± 0·5 pulses/6 h, P<0·01) and amplitude (15·2 ± 4·6 pmol/l, P<0·05) of the GnRH pulses decreased. During positive feedback, there was a large surge in the concentration of GnRH, due primarily to an increase in pulse frequency (11·0±1·3 pulses/6 h, P<0·01). A change in pulse amplitude was not detected, but there was a large increase in the basal level of GnRH (P<0·05). As a consequence of the changes in frequency and amplitude of the pulses, the mean levels of GnRH before injection with oestradiol (5·3 ± 1·0 pmol/l) differed (P<0·05) from those during negative (3·8±0·5 pmol/l) and positive (18·9±4·7 pmol/l) feedback phases.

These results show that the biphasic pattern of LH secretion induced by oestrogen injection in short-term ovariectomized ewes is caused by parallel changes in the secretion of GnRH as well as changes in pituitary responsiveness to GnRH. An abrupt increase in the frequency of GnRH pulses appears to be a key component of the positive feedback mechanism which elicits the oestradiol-induced surges of both GnRH and LH.

Journal of Endocrinology (1989) 123, 375–382
Quantitative analysis of germ cell numbers and relation to intratesticular testosterone following vitamin A-induced synchronization of spermatogenesis in the rat
Authors: Bartlett J. M. S. , Weinbauer G. F. , Nieschlag E.
Published: December 2008

Synchronization of spermatogenesis would provide an ideal model for the investigation of stage-dependent changes in the secretion of paracrine factors. In vitamin A-deficient animals subsequently injected with vitamin A, over 80% of seminiferous tubules were synchronized within three to five stages of the seminiferous cycle. Following replenishment of vitamin A, spermatogenic stages IV–VI (35 days), VI–VIII (38 days), IX–XII (41 days), I–IV (45 days) and V–VII (48 days) were observed. Despite synchronization of spermatogenesis at all stages, spermatogenesis was markedly impaired when evaluated in a quantitative fashion. At all times evaluated, numbers of round spermatids were reduced compared with age-matched controls. Numbers of pachytene spermatocytes reached control values only after 45 days of vitamin A replenishment. Elongate spermatids were almost totally absent up to 41 days after vitamin A replenishment. Testicular and epididymal weights were also reduced, although testicular weights showed a significant recovery over the time-course of the study. Serum and pituitary concentrations of LH and FSH were raised at the commencement of the study, with serum gonadotrophins returning to control values 48 days after vitamin A replenishment. Both testicular and serum testosterone concentrations in treated animals tended to be higher than in the controls.

Although synchronization of spermatogenesis was achieved, testicular testosterone concentrations did not reflect the stage-dependent cyclical changes observed in earlier studies. Testicular concentrations of testosterone were raised throughout the period of observation with the exception of animals synchronized around stages II–IV of the spermatogenic cycle. No correlation between the most frequent stages and intratesticular testosterone was found (r = 0·06, P > 0·1). Previous observations that testosterone concentrations are selectively increased at stages VII–VIII of the spermatogenic cycle are not supported by the present study.

Journal of Endocrinology (1989) 123, 403–412
Asymmetric ovulatory response induced by a unilateral implant of atropine in the anterior hypothalamus of the cyclic rat
Authors: Cruz M. E. , Jaramillo L. P. , Domínguez R.
Published: December 2008

The effects were analysed, on ovulation at the next oestrus, of unilaterally implanting atropine in the anterior hypothalamus of rats on each day of the oestrous cycle. Implantation on day 1 of dioestrus on either side of the anterior hypothalamus blocked ovulation. Implantation on the left side of the hypothalamus on day 2 of dioestrus blocked ovulation in all animals, whereas implantation on the right side allowed 71% of the animals to ovulate (0/4 vs 5/7; P < 0·05). Implantation at pro-oestrus on either side of the hypothalamus did not modify the rate of ovulation. When implantation was carried out on the day of oestrus on the right, none of the animals ovulated, but all ovulated when the implant was on the left (0/8 vs 8/8; P < 0·01). The results suggest the existence of a cholinergic hypothalamic lateralization in the mechanism regulating ovulation which depends on the day of the oestrous cycle.

Journal of Endocrinology (1989) 123, 437–439
Parathyroid hormone-related proteins in cultured epithelial cells
Authors: Docherty H. M. , Dixon-Lewis M. J. , Milton P. G. , Blight A. , Heath D. A.
Published: December 2008

The distribution and molecular characteristics of parathyroid hormone-related protein (PTH-rP) in conditioned media and cell extracts of cultured human keratinocytes, and in media from a variety of both normal and transformed epithelial and non-epithelial cell cultures were studied. PTH-rP of Mr 20 000 was observed in keratinocyte-conditioned media, and a larger form, Mr 29 000, in the keratinocyte cell extract. PTH-like bioactivity was also detected in media from 12 out of 17 epithelial cell cultures, but was not present in media from 14 cell cultures of non-epithelial origin. The molecular size of the PTH-like protein present in the epithelial cell media was approximately 20 000, corresponding with the PTH-rP in keratinocyte-conditioned medium. These observations may explain why hypercalcaemia is most commonly associated with tumours of epithelial origin.

Journal of Endocrinology (1989) 123, 487–493
Aldosterone and thyroid hormone interaction on the sodium and potassium transport pathways of rat colonic epithelium
Authors: Edmonds C. J. , Willis C. L.
Published: December 2008

The effect of hypothyroidism on potassium adaptation (shown by increased potassium secretion in response to potassium loading) and on the action of aldosterone on potassium secretion and sodium fluxes was examined in the rat distal colon.

Potassium adaptation, particularly the response to an acute potassium load, was impaired by hypothyroidism which also considerably reduced the rise of transepithelial electrical potential difference (p.d.) of total and transcellular (active) lumen-to-plasma sodium fluxes and of potassium secretion normally produced by aldosterone. These changes were, in part, corrected by a short period (3 days) of tri-iodothyronine replacement. Moreover in aldosterone-treated hypothyroid rats, amiloride in the lumen was considerably less effective in reducing the p.d. and sodium fluxes than in aldosterone-treated normal rats.

The intracellular sodium transport pool was greater in the hypothyroid than in the normal rats (5·0± 1·1 (s.e.m.) nmol/mg dry weight compared with 2·9 ± 0·2 nmol/mg dry weight; P<0·02). Aldosterone increased the pool in the normal but not in the hypothyroid rats while amiloride had little effect on the pool in the aldosterone-treated hypothyroid rats but almost abolished it in aldosterone-treated normal rats.

Aldosterone plays a major part in the adaptation of colonic sodium and potassium transport to sodium depletion or potassium excess; these adaptations were much impaired in hypothyroid animals. The present results are consistent with a deficiency in aldosterone induction of potassium- and amiloride-sensitive sodium pathways in the apical membrane of colonic epithelial cells in hypothyroid rats, a deficiency which limits the stimulant effect of aldosterone on sodium and potassium transport.

Journal of Endocrinology (1990) 124, 47–52
Inhibition by staurosporine of TRH-induced refractoriness of inositol phospholipid hydrolysis in rat anterior pituitaries
Authors: Iriuchijima T. , Mori M.
Published: December 2008

To clarify the mechanism(s) underlying the TRH-induced refractory state of the anterior pituitary, we evaluated rat pituitary inositol phospholipid hydrolysis in the presence of staurosporine. TRH caused a time- and dose-dependent accumulation of inositol phosphates in rat anterior pituitary slices. Pretreatment with 550 nmol TRH/l completely abolished the subsequent accumulation of inositol phosphates in response to 140 nmol TRH/l. TRH-stimulated accumulation of inositol phosphates did not occur after pretreatment with 0·2 μmol phorbol ester/l. Refractoriness of inositol phospholipid hydrolysis which was produced by pretreatment with TRH and phorbol ester was inhibited by staurosporine. The present data support the hypothesis that protein kinase C plays a profound role in TRH induction of the refractory state of inositol phospholipid hydrolysis in the anterior pituitary.

Journal of Endocrinology (1990) 124, 75–79
Central administration of corticotrophin-releasing factor in the sheep: effects on secretion of gonadotrophins, prolactin and cortisol
Authors: Naylor A. M. , Porter D. W. F. , Lincoln D. W.
Published: December 2008

Stress interferes with the normal secretion of LH and FSH from the anterior pituitary gland and therefore exerts a deleterious effect on reproductive function. Evidence suggests that the stress-induced disruption of gonadal function is due to a central action of corticotrophin-releasing factor (CRF) to inhibit the release of LHRH into the hypophysial-portal circulation. The following studies were undertaken to investigate further the role of CRF in regulating gonadotrophin release in the sheep and to determine whether central administration of this peptide can alter the secretion of other hormones (e.g. prolactin and cortisol) known to be released under conditions of stress.

In contrast to other species, injection of CRF into the third ventricle of the sheep brain caused a dose-related stimulation of LH secretion. The pulse frequency and mean levels of LH were increased significantly following central administration of CRF. In contrast to this effect, central administration of CRF did not alter the plasma concentration of FSH but caused a marked and dose-related stimulation of prolactin and cortisol secretion. The stimulatory effect of CRF on prolactin secretion was reversed by i.v. administration of the opioid antagonist naloxone, suggesting that endogenous opioid peptides mediate the central effect of CRF on the release of prolactin, but not cortisol.

In conclusion, these data demonstrate that administration of CRF causes a dose-related stimulation of LH and prolactin release from the anterior pituitary gland and cortisol from the adrenal gland. In the case of prolactin, endogenous opioid peptides are likely to mediate this response. The observations concerning LH are the opposite of those reported for the rat and the monkey where CRF caused a prolonged inhibition of gonadotrophin secretion. This suggests that a species difference may exist or, alternatively, the stimulatory effect of CRF on LH secretion in the sheep may be similar to the increase in LH secretion reported in rats and monkeys subjected to short-term handling or restraint stress.

Journal of Endocrinology (1990) 124, 117–125
The decreased plasma concentration of insulin-like growth factor-I in protein-restricted rats is not due to decreased numbers of growth hormone receptors on isolated hepatocytes
Authors: Thissen J. P. , Triest S. , Maes M. , Underwood L. E. , Ketelslegers J. M.
Published: December 2008

The resistance to GH and the low serum concentrations of insulin-like growth factor-I (IGF-I) that occur during fasting are accompanied by decreased GH receptors in liver homogenates. In protein restriction, however, serum IGF-I but not GH receptors are decreased, suggesting that a post-receptor defect exists. Because conclusions about the status of GH receptors during dietary manipulation are based on studies using liver homogenates, the present study was undertaken to determine whether changes in GH binding by homogenates are paralleled by changes in receptors on the cell surface considered to mediate the GH signal. Collagenase-dispersed hepatocytes or liver homogenates from 7-week-old female Wistar rats fed various diets were evaluated for changes in somatogenic receptors. Fasting for 24 h reduced significantly (P< 0·001) the plasma concentrations of IGF-I (−31%). Likewise, GH-binding sites were decreased on hepatocytes (−55%; P<0·01) and in liver homogenates (−60%; P < 0·001) compared with controls, as was the velocity of initial binding (−77%; P<0·001).

Protein restriction for 1 week decreased plasma concentrations of IGF-I (−42%; P< 0·001) but GH-binding sites were not significantly reduced on hepatocytes or in homogenates. The velocity of initial binding was also not decreased. We conclude that observations on changes in homogenate binding of bovine GH during dietary manipulation provide a reliable means of assessing changes in cell-surface GH receptors. The absence of a decline in surface binding during feeding of a low-protein diet supports the hypothesis that the decline in IGF-I during protein restriction is mediated by post-receptor events.

Journal of Endocrinology (1990) 124, 159–165
Maternal modulation of growth hormone secretion in the neonatal rat: involvement of mother–offspring interactions
Authors: Kacsoh B. , Meyers J. S. , Crowley W. R. , Grosvenor C. E.
Published: December 2008

Serum GH levels increased in 2- or 8-day-old rat pups when sucking mammary glands whose main milk ducts were ligated. Although intragastric administration of rat milk has been shown to increase serum GH levels in neonatal rats, ingestion of milk during suckling did not increase serum GH values further. In another experiment, 2-day-old pups obtained no milk when they were suckled by anaesthetized mothers, and in this instance the serum GH concentration of the pups decreased. This decrease was prevented if the mothers were injected with oxytocin to counteract the depressant effect of the anaesthesia on milk ejection; nevertheless, GH levels in neonatal animals failed to increase following suckling. Thus some aspect of maternal activity appears to be involved in the suckling-induced increase of serum GH in rat pups. To elucidate which components of maternal activity might be involved, the effects of manipulations of ambient temperature as well as stimulation of the oral or anogenital regions were examined. Exposing rat pups to 37 °C (nest temperature) during the 6-h separation period before suckling prevented the separation-induced decrease in serum GH levels of 2-day-old pups. Moreover, exposure to 37 °C for 30 min following a 6-h separation at room temperature (22 °C) mimicked the effect of suckling in increasing serum GH levels in the pups. Suckling following separation at 37 °C was unable to increase serum GH values further. In other studies, stimulation of the oral zone (feeding from a soft cannula) or anogenital zone (inducing urination and defecation with a wet brush) of the pups significantly decreased neonatal serum GH values. The painful stimulus of administration of s.c. hyperosmotic saline was without effect on serum GH levels.

In summary: (1) suckling, even without milk removal, increases serum GH levels in neonatal rats; (2) some aspect of maternal activity is involved in the suckling-induced increase of serum GH concentration in the neonate; (3) provision of a warm ambient temperature by the mother is a critical component of this maternal activity; (4) the effects of milk and the maternal activity associated with suckling are not additive in increasing serum values of GH in neonatal rats; and (5) oral feeding is not a suitable approach for studying the effects of milk on serum GH in neonatal rats.

Journal of Endocrinology (1990) 124, 233–240