Ovulation is a major target for the control of fertility and infertility in humans and animals. Several neuropeptides and neurotransmitters, i.e., neuropeptide Y, b-endorphin, norepinephrine (NE), gamma aminobutyric acid and acetylcholine, influence the preovulatory secretion pattern of gonadotropin-releasing hormone (GnRH). The magnitude of gene transcription/translation in the neurons that express these chemicals may identify how and where they modulate GnRH release. To test this hypothesis, we utilized the expression of the early oncogene, cfos, as a marker to locate the onset of gene transcriptional events in brainstem and hypothalamus during the preovulatory GnRH surge. Coitus in female rabbits, like estrogen in monkeys, induces NE/GnRH release at a predicted time after the stimulus. Thus, rabbits were killed and their brains fixed by paraformaldehyde infusion at times before and 15-, 30-, 60-, 90- and 120-min after coitus for cfos mRNA quantitation using in s itu hybridization. Within 30 minutes after coitus, several noradrenergic-associated brainstem nuclei, lateral tegmentum (A1), nucleus of the solitary tract (A2) and locus coeruleus (A6) exhibited enhanced cfos mRNA expression in females. Also, two nuclei in the medulla oblongata that send projections to A6, the nucleus of praepositus hypoglossy and the paragigantocellular nucleus, showed increased c-fos expression only in coitally activated females. The septum also showed heavier 35S-cfos label by 30 min after coitus than septum from unmated control females. In the hypothalamus the anteroventral periventricular area (AVPV), arcuate, paraventricular and medial preoptic area showed enhanced cfos mRNA expression between 15 and 60 minutes postmating. The AVPV showed the most concentrated cfos expression. Whether these times after coitus and transcriptional changes in cfos signals can be utilized for predictions of where and how coital stimulation triggers NE/GnRH release is unclear, but these data are encouraging. Because a massive release of hypothalamic NE and a two-fold increase in brainstem NE (A6) gene expression occurred around the time of the estrogen-induced hypothalamic GnRH release, we suggest that the signaling mechanisms in rabbits may be useful in understanding those in primates. FUNDING NIH HD30316, HD18185 PUBLICATIONS None
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