Effects of glucocorticoids on pituitary hormonal responses to hypoglycemia. Inhibition of prolactin release.

The characteristics of pituitary hormonal responses to insulin-induced hypoglycemia were investigated in 16 normal men. In all subjects, levels of blood sugar fell below 35 mg/100 ml. A statistically significant increase in mean plasma levels of prolactin, ACTH, cortisol and growth hormone was observed. Prolactin levels increased in all subjects but one; individual peak values were 1.4 minus 8.4 times greater than base levels. The kinetics of prolactin, GH and ACTH responses were similar; in particular, the onset of release (25 min) of prolactin, GH and ACTH was similar. After dexamethasone administration, insulin tolerance tests wererepeated in a number of subjects using adequate amounts of insulin to achieve hypoglycemia equivalent to that obtained in the control experiments. The administration of 1 mg of dexamethasone the evening before the test suppressed basal levels of ACTH and cortisol and the ACTH-but not the cortisol-response to hypoglycemia. Both basal levels of prolactin and prolactin response to hypoglycemia were significantly lowered but growth hormone response was not modified by administration of 1 mg of dexamethasone. The administration of larger doses of dexamethasone (1 mg every 6 h for 2 days) almost completely suppressed basal levels of ACTH, cortisol and prolactin, as well as the hypoglycemia-induced release of these hormones. In contrast, the growth hormone response to hypoglycemia was only partially inhibited. These findings demonstrate that both basal secretion and hypoglycemia-induced release of prolactin, ACTH, cortisol and growth hormone are suppressible by glucocorticoids.

The endocrinometabolic effects of beclomethasone dipropionate in asthmatic patients.

The endocrinometabolic effects of the aerosol administration of beclomethasone dipropionate (100 microng four times daily) were evaluated in 20 asthmatic patients (11 corticodependent and nine noncorticodependent) during one month. In the noncorticodependent group, aerosol administration of beclomethasone had no statistically significant effect on the results of the glucose tolerance test and the plasma levels of insulin; there was a slight decrease in basal levels of cortisol, but the response of the cortisol level to administration of ACTH remained quite normal. In corticodependent patients, after substitution of aerosol therapy with beclomethasone for the oral therapy with steroids, the depression of adrenal function disappeared, usually quickly (in less than one month), whereas the abnormalities in the results of the glucose tolerance test persisted. Thus, at the dosage used, beclomethasone dipropionate might have minor systemic endocrinometabolic effects.

Seasonal, circadian and episodic variations of human immunoreactive beta-MSH, ACTH and cortisol.

The 24-hour profile of plasma levels of immunoreactive beta-MSH (IR-beta MSH), ACTH and cortisol was obtained at 15-min intervals in six normal males in summer and winter. In the radioimmunoassay used, dilution curves of human beta-MSH and human beta-LPH were not parallel. A seasonal variation in basal pituitary-adrenal secretion, with higher levels in winter than in summer, was demonstrated. A circadian rhythm was found to be significant for ACTH, IR-beta MSH and cortisol in all investigations. Whereas ACTH and cortisol patterns were largely concordant in all studies, there was a significant desynchronization of the circadian rhythm of IR-beta MSH as compared to ACTH in five cases. Eighty-three percent of the secretory spikes of cortisol but only 68% of the IR-beta MSH spikes were concomitant with an ACTH spike. Correlations between maximal levels of concomitant spikes were higher during the quiescent period of pituitary-adrenal secretion (22.00--04.00) for ACTH-cortisol whereas for ACTH-IR-beta MSH, highest correlations were found during the active early morning secretory phase (04.00--10.00). For the three plasma constituents studied, longer apparent half-lives were found to occur when the basal level before spiking was already elevated, suggesting that ACTH, beta-LPH and cortisol are secreted in bursts superimposed on a continuous basal secretion. Absolute increments of concentration appeared to be relatively independent of the level before spiking. It is suggested that the dissociations between ACTH and IR-beta MSH fluctuations in plasma observed here result from in vitro proteolysis of beta-LPH.

Acute endocrine profile of sulpiride in the human.

Normal men and normally menstruating women received i.m. injections of 0.1 to 4.0 mg/kg sulpiride. This psychotropic drug induced a very rapid (already significant after 5 minutes) and sustained (still significant after 7 hours) elevation of prolactin (PRL) concentrations in all subjects with no consistent modification of LH and FSH. After injection of 4.0 mg/kg, there was similarly no modification of mean TSH concentrations in the women tested in the luteal phase, as well as of mean GH levels in men. Sulpiride prevented the inhibitory effect on PRL levels of 500 mg levodopa, administered orally simultaneously; levodopa administered 2 hours prior to sulpiride failed to counteract the PRL-stimulatory effect of sulpiride. Under chronic sulpiride-induced hyperprolactinaemia, levodopa exhibited however a very slight inhibitory effect on PRL concentrations. These data are in agreement with the hypothesis that sulpiride acts mainly at the pituitary level by blocking dopamine receptors of the lactotropes and support the concept that the menstrual cycle perturbations observed under chronic sulpiride administration result from hyperprolactinaemia itself or from a mechanism quite similar to that by which sulpiride induces hyperprolactinaemia.

Simultaneous study of cortisol, growth hormone and prolactin nyctohemeral variations in normal and obese subjects. Influence of prolonged fasting in obesity.

Hourly integrated concentrations (IC) of growth hormone (GH), prolactin (PRL) and cortisol were determined by a continuous sampling procedure in six obese women, before and at the end of a 12 day fast, and in eight normal controls under basal conditions. Hormonal 24 h IC and nyctohemeral variations were calculated from these data. Nyctohemeral rhythms were investigated by the periodogram method. A significant increase over basal values of 24 h IC of PRL, GH and cortisol was observed at the end of the fasting period. Nyctohemeral variations--but not nyctohemeral rhythm--of IC-GH were found in normal subjects. They were abolished in obese patients under basal conditions but restored during fasting. The circadian rhythm of cortisol was not altered in obesity. A shift of the normal nyctohemeral rhythm of PRL was observed in obese patients, but the normal pattern was restored during fasting.

Pituitary and extrapituitary effects of somatostatin in normal man.

The effects of synthetic linear somatostatin on basal circulating levels on several pituitary and pancreatic hormones, and of glucose and free fatty acids (FFA) were studied in 6 normal men after an overnight fast. A priming intravenous infusion of 250 mug of somatostatin in 18 sec was followed by a constant infusion of 500 mug over a period of 60 min. A decrease in plasma values of GH, prolactin, TSH, insulin and glucagon and in blood glucose was observed during somatostatin infusion, while FFA levels increased progressively. Plasma IRI and blood glucose increased rapidly when the somatostatin infusion was stopped, while FFA decreased progressively; GH, prolactin, TSH and glucagon remained low as compared to basal levels for one hour after the end of the infusion, i.e. until the end of the experiment. A slight but significant increase of LH and ACTH was observed after the end of the infusion.