title: Detailed examination of the mechanism and site of action of progesterone and corticosteroids in the regulation of gonadotropin secretion: hypothalamic gonadotropin-releasing hormone and catecholamine involvement.
abstract: Progesterone and certain corticosteroids, such as deoxycorticosterone (DOC) and triamcinolone acetonide (TA), can stimulate gonadotropin surges in rats. The mechanism of these steroids could involve a pituitary or hypothalamic site of action, or both. Progesterone and TA did not alter the ability of GnRH to release LH or FSH either before, during, or after the gonadotropin surge induced by these steroids in estrogen-primed ovariectomized female rats. Furthermore, progesterone, TA and DOC were unable to induce a gonadotropin surge in short-term estrogen-primed castrated male rats. These results suggested a hypothalamic rather than a pituitary site of action of progesterone and corticosteroids in the release of gonadotropins. Since progestin and corticosteroid receptors are present in catecholamine neurons, a role for catecholamine neurotransmission in progesterone and corticosteroid-induced surges of LH and FSH in estrogen-primed ovariectomized rats was examined. Catecholamine synthesis inhibitors and specific alpha 1 (prazosin), alpha 2 (yohimbine), and beta (propranolol) receptor antagonists were used to determine the role of catecholamine neurotransmission in the steroid-induced surges of LH and FSH. Both of the catecholamine synthesis inhibitors, alpha-methyl-p-tyrosine HCl (alpha-MPT), a tyrosine hydroxylase inhibitor, and sodium diethyldithiocarbamate (DDC), an inhibitor of dopamine-beta-hydroxylase, attenuated the ability of progesterone, TA, and DOC to induce LH surges when administered 3 h and 1 h, respectively, before the steroid. DDC also suppressed the ability of progesterone, TA, and DOC to induce FSH surges. Rats treated with alpha-MPT had lower mean FSH values than did steroid controls, but the effect was not significant. Both the alpha 1 and alpha 2 adrenergic antagonists, prazosin and yohimbine, significantly suppressed the ability of progesterone, TA, and DOC to induce LH and FSH surges. In contrast, the beta adrenergic receptor blocker, propranolol, had no effect upon the ability of progesterone, TA, or DOC to facilitate LH and FSH secretion. Finally, the stimulatory effect of progesterone and TA upon LH and FSH release was found to be blocked by prior treatment with a GnRH antagonist, further suggesting hypothalamic involvement. In conclusion, this study provides evidence that the stimulation of gonadotropin release by progesterone and corticosteroids is mediated through a common mechanism, and that this mechanism involves the release of GnRH, most likely through catecholaminergic stimulation. Furthermore, catecholamine neurotransmission, through alpha 1 and alpha 2 but not beta receptor sites, is required for the expression of progesterone and corticosteroid-induced surges of LH and FSH in estrogen-primed ovariectomized rats.
authors.affiliation: Department of Physiology and Endocrinology, Medical College of Georgia, Augusta 30912.
authors.forename: D W
authors.initials: DW
authors.lastname: Brann
authors.forename: V B
authors.initials: VB
authors.lastname: Mahesh
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D002369:Castration; D003900:Desoxycorticosterone / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology; D006065:Gonadotropins, Pituitary / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014222:Triamcinolone Acetonide / Q000494:pharmacology
chemical_list: D000305:Adrenal Cortex Hormones; D006065:Gonadotropins, Pituitary; D007987:Gonadotropin-Releasing Hormone; D003900:Desoxycorticosterone; D011374:Progesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D014222:Triamcinolone Acetonide