Progesterone diminishes the sensitivity of gonadotropin-releasing hormone-stimulated luteinizing hormone (LH) release and protects an LH pool from desensitization: actions opposed by cholera toxin.
In the present study we used characterized perifusion model for the development of homologous desensitization to GnRH in the pituitary gonadotrope. This system relies on immobilized primary pituitary cultures that are perifused with various pulse patterns and concentrations of GnRH; these patterns and concentrations are selected to maintain, inhibit, restore, circumvent the desensitization process. The data indicate that progesterone (P) inhibits LH release in response to pulsatile administration of GnRH; this effect is blocked by the P antagonist, RU486, and is opposed by cholera toxin, an agent that provokes the formation of cAMP. In multiple and rapid pulse administration of 5 nM GnRH, which is usually associated with desensitization, the area under the LH release curve is progressively diminished when cells are preincubated with medium only or with medium containing cholera toxin. In contrast, cells pretreated with P are less responsiveness to GnRH, but maintain a relatively constant level of LH release (area under the curve). These data suggest a modulatory role for P in the development of the desensitized state and indicate that P can functionally protect a pool of LH from the onset of desensitization.
Janovick
J A
JA
Orgeon Regional Primate Research Center, Beaverton 97006, USA.
Conn
P M
PM
D000818:Animals; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology*; D004361:Drug Tolerance; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism*; D015735:Mifepristone / Q000494:pharmacology; D010477:Perfusion; D010507:Periodicity; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats
D006727:Hormone Antagonists; D015735:Mifepristone; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D007986:Luteinizing Hormone; D002772:Cholera Toxin