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SUMMARY

The existence of a circadian rhythm in the sensitivity of the hypothalamus of the laying hen to stimulation by progesterone was investigated by injecting 0·5 mg progesterone subcutaneously during the proposed period of maximum insensitivity. Following this treatment increases in plasma concentrations of both LH and progesterone were observed which were comparable to the spontaneous preovulatory rises in the plasma levels of the hormones.

The ability of either progesterone or luteinizing hormone releasing hormone (LH-RH) to induce premature ovulation varied according to the stage of follicular development. Neither hormone was more than 28% effective when injected within 6·5 h of the previous ovulation, whereas both hormones were 100% effective approximately 27 h after the terminal ovulation of a clutch sequence. Failure to ovulate in response to LH-RH given 6·5 h after ovulation was associated with a lack of progesterone secretion.

Both LH and progesterone were secreted when ovulation was induced by injections of either LH-RH or progesterone, and LH was secreted in response to progesterone given 6·5 h after ovulation. These results demonstrate that progesterone stimulates the secretion of LH and LH stimulates the secretion of progesterone. The precise physiological role of these two hormones, however, was not established.

SUMMARY

Blood samples were taken every 3 h, over a 27 h period, from (1) a group of 12 intact male quail on short days (lights on 09.00–17.00 h) and during the 2nd, 15th and 36th day of photostimulation (lights on 09.00–05.00 h); (2) 12 castrated male quail on the 2nd, 20th and 43rd long day, and (3) 12 intact male quail on the 12th long day. Plasma LH was measured in all samples and FSH in the 43rd long day castrate and 12th long day intact male samples. Although there was considerable variation in the levels of LH and FSH, both between birds and between samples taken from the same bird, statistical analyses failed to reveal any diurnal (or circadian) rhythm at any time. There was a marked correlation between the LH and FSH levels in all samples.

Possible episodic LH secretion was investigated by taking blood samples every 15 min for between 3 and 6 h from six intact male quail and six laying females on long days. Samples were obtained from each bird at three time-periods which were arranged so as to overlap and cover the first 12 h of the daily photoperiod. Statistical analysis suggested that episodes of secretion occurred 6–10 times/day in males, and 4–8 times/day in females. The pulses appeared to occur at random.

SUMMARY

The plasma sugar, 11-hydroxycorticosteroid, and growth hormone responses to insulin have been studied in patients with Cushing's disease. They showed an impaired or absent plasma 11-hydroxycorticosteroid and growth hormone rise during the test, as compared with control subjects, despite the injection of amounts of insulin which produced a similar degree of hypoglycaemia. This test proved of value in differentiating between these patients and those with 'simple ' obesity since the latter usually showed a normal growth hormone and adrenal response provided an adequate amount of insulin was administered.

The patients with Cushing's disease also had an impaired adrenal response to pyrogen and to dexamethasone administration and failed to show a normal plasma 11-hydroxycorticosteroid circadian rhythm. Their response to corticotrophin, lysine vasopressin, and metyrapone, however, was normal or enhanced. It is suggested that these findings imply an abnormality of hypothalamic or cerebral control and not a primary defect of pituitary function as proposed originally by Harvey Cushing.

The growth hormone response to insulin remained impaired in four out of six patients totally adrenalectomized for Cushing's disease but was normal in three patients adrenalectomized for other reasons. It is suggested that the defect which impairs the adrenal response to insulin may, on occasions, also impair the mechanism normally operative for growth hormone secretion.

ABSTRACT

We studied 24-h hormone profiles and hormonal responses to insulin-induced hypoglycaemia prospectively in 23 children of similar age and pubertal stage, nine of whom had received prior cranial irradiation (group 1) and fourteen of whom had not (group 2), before and 6–12 months after total body irradiation (TBI) for bone marrow transplantation in leukaemia.

Fourier transformation demonstrated that group 1 children had a faster periodicity of GH secretion before TBI than group 2 children (160 vs 200 min) but the amplitude of their GH peaks was similar. There were no differences between the groups in circadian cortisol rhythm, serum concentrations of insulin-like growth factor-I (IGF-I), sex steroids and basal thyroxine (T₄). The peak serum GH concentrations observed after insulin-induced hypoglycaemia were similar between the two groups but the majority of patients had blunted responses.

TBI increased the periodicity of GH secretion in both groups (group 1 vs group 2; 140 vs 180 min), but the tendency to attenuation of amplitude was not significant. There were no significant changes in the peak serum GH concentration response to insulin-induced hypoglycaemia which remained blunted. Serum IGF-I, sex steroid, cortisol or T₄ concentrations were unchanged.

Low-dose cranial irradiation has an effect on GH secretion affecting predominantly frequency modulation leading to fast frequency, normal amplitude GH pulsatility. This change is accentuated by TBI. In patients with leukemia, there is a marked discordance between the peak serum GH response to insulin-induced hypoglycaemia compared with the release of GH during 24-h studies, irrespective of the therapeutic regimen used. Pharmacological assessment of GH reserve needs to be interpreted with caution in such situations.

Journal of Endocrinology (1993) 136, 331–338

ABSTRACT

Male Wistar-derived rats (200–250 g) were treated for 14 days with prednisolone 21-sodium succinate at a concentration of 1035 μmol/l in their drinking water. The drug was then replaced with normal tap water and groups of animals were killed at various times during recovery, trunk blood being collected after decapitation. At the same time, hypothalamic slices, anterior pituitary gland fragments and adrenals were removed and their responsiveness assessed by exposure to appropriate stimuli in vitro. Tissues were also extracted to measure changes in content of hormones during recovery. Treatment with prednisolone produced marked reductions in body weight gain, adrenal weight and pituitary ACTH content, but no significant change in hypothalamic corticotrophin-releasing factor (CRF) bio- or immunoreactivity. The ACTH content was restored by 5 days after withdrawal but adrenal weight remained significantly reduced after 9 days of recovery. The responsiveness of the hypothalamus to acetylcholine in vitro was markedly inhibited and was still significantly reduced 7 days after withdrawal. The responsiveness of the anterior pituitary gland to synthetic CRF or arginine vasopressin and that of the adrenal gland to ACTH added in vitro were restored simultaneously after 7 days of withdrawal. In vivo, recovery was assessed by measurement of the response to laparotomy stress. Treatment with prednisolone prevented the increase in the plasma concentrations of ACTH and corticosterone produced by stress, and these responses recovered by 5 days (corticosterone) and 7 days (ACTH) after withdrawal. The abolition of the circadian rhythms of ACTH and corticosterone by treatment was also reversed by 5 days after withdrawal. This pattern of recovery is different from that which we observed after long-term treatment with dexamethasone, where the responsiveness of the hypothalamus and adrenal gland in vitro recovered before that of the anterior pituitary gland.

J. Endocr. (1987) 113, 239–247

ABSTRACT

The aim of the present work was to study the relationship between sex hormones and plasma renin levels during the oestrous cycle in a Wistar-derived rat strain. Plasma renin activity (PRA) as well as plasma renin concentration (PRC) were increased during the day of oestrus in rats with controlled 4-day oestrous cycles. This increase in PRA and PRC was not found when rats were ovariectomized on dioestrus day 2 and samples measured on the expected day of oestrus. The increase in PRA and PRC was not found when normal cyclic rats were treated with either tamoxifen or the progesterone receptor blocker RU 38486. Treatment with progesterone at pro-oestrus after ovariectomy on dioestrus day 2 partially increased the PRA and PRC when compared with the values found during the day of oestrus in control rats. The combined treatment of ovariectomized rats on dioestrus day 2 with oestrogen and progesterone restored the normal increase in PRA and PRC values on the expected day of oestrus. We therefore postulate that the sodium diuresis promoted by progesterone may be modulated by the previous peak of oestrogen. However, stimulation of extrarenal sources of renin cannot be excluded nor can an involvement of inactive precursors of renin in the fluctuations of active renin that occur during the oestrous cycle. No important change in plasma renin substrate (PRC) was observed during the oestrous cycle. PRA, PRC and PRS were determined every 4 h during the 4-day oestrous cycle. Our results clearly show a rhythmic variation in PRA and PRC which increases during the day of oestrus with a peak at 06.00 h. No circadian variation related to the sleep-wakefulness rhythm or other regular daily changes in PRA, PRC or PRS was found.

Journal of Endocrinology (1989) 121, 261–267

In order to determine the temporal relationships between variations in 5-hydroxy-tryptamine (5-HT, serotonin) metabolism in the suprachiasmatic nucleus (SCN) and the cyclic LH surge, and also to check whether implantation of oestradiol capsules might modulate 5-HT metabolism in the SCN, we carried out a parallel study of 5-HT content in the SCN and median eminence, and 5-HT metabolism in the SCN and supraoptic region in vitro. These experiments were performed on intact male rats, ovariectomized females and ovariectomized females implanted with oestradiol.

It was only in ovariectomized rats implanted with oestradiol, in which we have described the existence of a clear-cut circadian rhythm of LH secretion, that we found fluctuations in the content, synthesis and utilization of 5-HT. The content and synthesis were characterized by a peak between 12.00 and 15.00 h, whereas utilization was 50% higher at 09.00 and 19.00 h than at 15.00 h. These fluctuations in 5-HT content and metabolism were specific to the SCN; the median eminence and the supraoptic region did not show such variations. They were also specific to ovariectomized rats implanted with oestradiol, since the patterns of 5-HT content and metabolism in the SCN were the same in males and ovariectomized females and did not differ from those in the median eminence, the supraoptic region or the whole hypothalamus.

These results suggest that 5-HT terminals in the SCN play an important role in the control of cyclic LH secretion at a critical period. Moreover, oestradiol seems to be partly responsible for the fluctuations of 5-HT metabolism in the SCN of ovariectomized rats implanted with oestradiol.

The secretion of corticotrophin releasing activity (CRA) from the isolated rat hypothalamus incubated in vitro was investigated under various conditions of incubation and of pretreatment of donor animals providing hypothalami. Media from hypothalamic incubations were assayed for CRA by a validated double in-vitro bioassay technique which differentiates CRA from vasopressin.

A circadian rhythm was found in the secretion of CRA in vitro from isolated hypothalami obtained from animals killed at different times of the day. Secretion of CRA increased significantly at 19.00 h (dusk) compared with the secretion rate at 07.00 h, in synchrony with a rise in plasma corticosterone levels. In addition, both plasma corticosterone concentrations and CRA secretion in vitro were higher at 07.00 h than at 19.00 h after exposure of the donor animals to a reversed light cycle for 7–10 days.

Hypothalami obtained from animals chronically treated with betamethasone in the drinking water showed a diminished secretion of CRA in vitro. Exposure of untreated animals to ether vapour for 2 min immediately before death significantly increased the subsequent secretion of CRA in vitro. Ether exposure did not significantly affect the secretion of CRA in vitro from hypothalami of betamethasone-treated rats. There was a close correlation between plasma corticosterone levels and in-vitro CRA release after these treatments. The results suggest that the secretion of CRA examined in this way is a phenomenon which can reflect the changes which occur in the activity of the hypothalamo-pituitary-adrenal system in vivo during the 24-h cycle, after glucocorticoid treatment and after ether stress.