Mechanism of Action of Hypothalamic Hormones in the Adenohypophysis

Abstract

The observation of a close parallelism between changes of cyclic adenosine 35 monophosphate (cAMP) accumulation and specific hormone release under the influence of 2 stimulatory hypothalamic hormones thyrotropin-releasing hormone (TRH) and luteinizing hormone-releasing hormone (LHRH) and 1 inhibitory peptide (somatostatin) strongly suggest that the adenylate cyclase system is involved in the mechanism of action of these 3 peptides in the anterior pituitary gland. The mechanism (depicted in a figure) is supported by data obtained on the characteristics of the TRH receptor and properties of adenohypophyseal cAMP-dependent protein kinase and its substrates. Estrogen treatment in vivo led to an increase in the number of adenohpophyseal TRH receptors whereas opposite effects were seen after thyroid hormone administration. In vitro pituitary cell primary cultures showed that estrogens stimualted both LH and follicle stimulating (FSH) hormone secretions while androgens had opposite effects on the secretion of the 2 hormones markedly inhibiting LH and stimulating FSH. The effect of progesterone in estradiol-primed cells was biphasic LH secretion whereas the effect on FSH secretion was exclusively stimulatory. Inhibin activity of ovarian and testicular origin was a potent inhibitor of basal FSH release. Recent data indicate that dopamine may be the main or even the only inhibitory substance of hypothalamic origin controlling prolactin secretion. Estrogens were found to stimulate the prolactin secretion directly at the pituitary level and to reverse the inhibitory effect of dopamine agonists on prolactin secretion.