Evidence for cAMP as a mediator of gonadotropin secretion from female pituitaries.
Sodium flufenamate, which inhibited gonadotropin-releasing hormone (GnRH)-stimulated increases in adenosine 3',5'-cyclic monophosphate (cAMP), was used to evaluate the potential role of cAMP as a mediator of GnRH-stimulated gonadotropin secretion. Quartered pituitaries from diestrous II female rats were perifused at 37 degrees C, and sequential effluent fractions were collected every 10 min. Administration of GnRH resulted in a characteristic biphasic response for both luteinizing hormone (LH) and follicle-stimulating hormone (FSH), whereas 5 microM cycloheximide inhibited the secondary augmented responses (phase II) of both hormones. Infusions of 0.1 mM flufenamate inhibited GnRH-stimulated gonadotropin secretion in a manner similar to that of cycloheximide, whereas the administration of 5 mM dibutyryl cAMP in combination with GnRH and flufenamate resulted in the restoration of LH and FSH secretion. The dibutyryl cAMP-restored response appeared to be protein synthesis dependent and specific for cAMP. These results suggest that although the cyclic nucleotide is not involved in the acute release of LH and FSH, it does appear to play a pivotal but indirect role in phase II release of the hormones, by effects involving the stimulation of de novo protein synthesis.
Bourne
G A
GA
Baldwin
D M
DM
D000249:Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D005439:Flufenamic Acid / Q000494:pharmacology; D006065:Gonadotropins, Pituitary / Q000378:metabolism*; D009994:Osmolar Concentration; D010906:Pituitary Hormone-Releasing Hormones / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics
D002087:Butyrates; D006065:Gonadotropins, Pituitary; D010906:Pituitary Hormone-Releasing Hormones; D020148:Butyric Acid; D000249:Adenosine Monophosphate; D005439:Flufenamic Acid; D003994:Bucladesine; D003513:Cycloheximide; D000242:Cyclic AMP; D004298:Dopamine