title: The negative feedback actions of progesterone on gonadotropin-releasing hormone secretion are transduced by the classical progesterone receptor.
abstract: Progesterone (P) powerfully inhibits gonadotropin-releasing hormone (GnRH) secretion in ewes, as in other species, but the neural mechanisms underlying this effect remain poorly understood. Using an estrogen (E)-free ovine model, we investigated the immediate GnRH and luteinizing hormone (LH) response to acute manipulations of circulating P concentrations and whether this response was mediated by the nuclear P receptor. Simultaneous hypophyseal portal and jugular blood samples were collected over 36 hr: 0-12 hr, in the presence of exogenous P (P treatment begun 8 days earlier); 12-24 hr, P implant removed; 24-36 hr, P implant reinserted. P removal caused a significant rapid increase in the GnRH pulse frequency, which was detectable within two pulses (175 min). P insertion suppressed the GnRH pulse frequency even faster: the effect detectable within one pulse (49 min). LH pulsatility was modulated identically. The next two experiments demonstrated that these effects of P are mediated by the nuclear P receptor since intracerebroventricularly infused P suppressed LH release but 3alpha-hydroxy-5alpha-pregnan-20-one, which operates through the type A gamma-aminobutyric acid receptor, was without effect and pretreatment with the P-receptor antagonist RU486 blocked the ability of P to inhibit LH. Our final study showed that P exerts its acute suppression of GnRH through an E-dependent system because the effects of P on LH secretion, lost after long-term E deprivation, are restored after 2 weeks of E treatment. Thus we demonstrate that P acutely inhibits GnRH through an E-dependent nuclear P-receptor system.
authors.affiliation: Institut National de la Recherche Agronomique, Neuroendocrinologie Sexuelle, Physiologie de la Reproduction des Mammiféres Domestiques, Nouzilly 37380, France. skinner@tours.inra.fr
authors.forename: D C
authors.initials: DC
authors.lastname: Skinner
authors.forename: N P
authors.initials: NP
authors.lastname: Evans
authors.forename: B
authors.initials: B
authors.lastname: Delaleu
authors.forename: R L
authors.initials: RL
authors.lastname: Goodman
authors.forename: P
authors.initials: P
authors.lastname: Bouchard
authors.forename: A
authors.initials: A
authors.lastname: Caraty
mesh_terms: D000818:Animals; D005246:Feedback; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007276:Injections, Intraventricular; D010052:Ovariectomy; D011374:Progesterone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000502:physiology*; D011980:Receptors, Progesterone / Q000502:physiology*; D012756:Sheep; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D011980:Receptors, Progesterone; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone