Effects of progesterone (P) and antiprogestin RU486 on LH and FSH release by incubated pituitaries from rats treated with the SERM LY11701 8-HCl and/or recombinant human FSH.
The aim of the present study was to investigate the role of the estrogen (ES) background on the effects of P or its antagonist RU486 on basal and LHRH-stimulated LH and FSH secretion. To do this, pituitaries collected from: intact rats in proestrus; rats injected with the ES antagonist LY11701 8-HCl; rats injected with recombinant-human FSH (r-hFSH) to stimulate ovarian hormonogenesis; and rats injected with both LY11701 8-HCl and r-hFSH were incubated with or without LHRH (10 nM) in the presence of P (100 nM) or RU486 (10 nM). RU486 decreased basal and LHRH-stimulated release of LH and FSH and LHRH self-priming in pituitaries from control rats, while P increased both pituitary responsiveness and LHRH self-priming. These effects were absent in pituitaries from rats treated either with the ES antagonist or r-hFSH, which, in the absence of P or RU486 in the incubation medium, reduced gonadotropin release. Because r-hFSH did not increase E2 serum concentration significantly, the putative FSH-dependent ovarian non-steroidal gonadotropin surge inhibiting factor (GnSIF) might be the hormonal cause of the reduced secretion of LH and FSH. Combined treatment with LY117018-HCl and r-hFSH had additive inhibitory effects on gonadotropin release. These results indicate that ES-inducible P receptor (PR) in the pituitary can be activated in a ligand-independent manner by intracellular messengers giving rise to enhanced basal and LHRH-stimulated gonadotropin secretion. The results also suggested that the r-hFSH-stimulated ovarian bioactive entity GnSIF and RU486 may share a similar mechanism of action involving pituitary PR.
Bellido
C
C
Department of Cell Biology, Physiology and Immunology, University of Córdoba, Spain.
Aguilar
R
R
Garrido-Gracia
J C
JC
Sánchez-Criado
J E
JE
D000818:Animals; D035061:Control Groups; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism* / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000378:metabolism*; D015735:Mifepristone / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
D006727:Hormone Antagonists; D011759:Pyrrolidines; D011994:Recombinant Proteins; D020845:Selective Estrogen Receptor Modulators; D013876:Thiophenes; D015735:Mifepristone; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; C025430:LY 117018; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone