Role of progesterone and nonsteroidal ovarian factors in regulating gonadotropin-releasing hormone self-priming in vitro.
We investigated the effects of gonadotropin surge-attenuating factor (GnSAF), inhibin, and follistatin on GnRH self-priming and its augmentation by progesterone. Two GnRH challenges, 60 min apart, were administered to rat pituitary monolayers after 90-min exposure to medium alone (control), progesterone, GnSAF, inhibin, or follistatin. Inhibin-stripped follicular fluid from superovulated women was used as a source of GnSAF bioactivity. Under control conditions, the greater response to the second GnRH challenge (peak 2, 9.2 +/- 2.1; peak 1, 4.4 +/- 0.9 ng LH/mL; P < 0.01) demonstrated GnRH self-priming. None of the treatments significantly altered the first LH peak. Progesterone markedly increased GnRH self-priming (peak 2, 12.6 +/- 2.5 ng LH/mL; P < 0.01). However, GnSAF and RU486 significantly reduced GnRH self-priming (peak 2, 4.6 +/- 0.9 and 5.6 +/- 1.6 ng LH/mL, respectively; P < 0.01). The augmentation of self-priming induced by progesterone was completely abolished by coincubation with either GnSAF or RU486 (peak 2, 7.5 +/- 1.6 and 4.3 +/- 0.9 ng LH/mL, respectively; P < 0.01). Neither inhibin nor follistatin had any effect on GnRH self-priming or its augmentation by progesterone. The actions of RU486 in the presence and absence of progesterone demonstrate a nonprogestagenic effect of RU486 on the gonadotropes. In conclusion, the suppression of GnRH self-priming, with or without progesterone augmentation, supports the hypothesis that GnSAF acts by maintaining the pituitary in an unprimed state of reduced responsiveness to GnRH.
Byrne
B
B
Department of Obstetrics and Gynecology, University of Aberdeen, Foresterhill, United Kingdom. b.byrne@ed_rbu.mrc.ac.uk.
Fowler
P A
PA
Templeton
A
A
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D015571:Follicular Fluid / Q000502:physiology; D038681:Follistatin; D006023:Glycoproteins / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D007265:Inhibins / Q000494:pharmacology*; D007700:Kinetics; D007986:Luteinizing Hormone / Q000378:metabolism*; D015735:Mifepristone / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D013480:Superovulation
D038681:Follistatin; D006023:Glycoproteins; D015735:Mifepristone; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D007265:Inhibins; D007986:Luteinizing Hormone