ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2006) 11 P678

Changes in GnRH gene expression in the medial basal hypothalamus of rhesus macaques across the menstrual cycle

HF Urbanski, N Noriega, VT Garyfallou, JL Downs & SG Kohama

Oregon National Primate Research Center, Beaverton, Oregon, United States.

Rhesus macaques, like humans, express two molecular forms of gonadotropin-releasing hormone (GnRH-I and GnRH-II). Although the role of GnRH-I in the control of the reproductive axis is well-established, the physiological role of GnRH-II is less clear. Both forms of GnRH are highly expressed in the monkey hypothalamus and both forms are highly effective at stimulating LH and FSH release in vivo. However, estradiol appears to affect GnRH-I and GnRH-II gene expression differentially, causing a suppression of the former and a stimulation of the latter, raising the possibility that GnRH-I and GnRH-II may have different reproductive roles. To examine this hypothesis, we isolated RNA from the medial basal hypothalamus (MBH) of female rhesus macaques at three different stages of the menstrual cycle (N=3/group): (1) the early follicular phase, when circulating estradiol and progesterone concentrations are low; (2) the late follicular phase, after the preovulatory estradiol peak while progesterone concentrations are still low; and (3) the mid-luteal phase, when circulating estradiol concentrations are low and progesterone concentrations are high. The samples were subjected to GeneChip microarray analysis (Affymetrix HG-U133A), and the data were analyzed using ANOVA and Newman-Keuls. Although expression of the GnRH-I gene was high in the MBH, it did not change across the menstrual cycle. In contrast, expression of GnRH-II gene in the MBH was low during the early follicular and mid-luteal phases but significantly (P<0.05) elevated during the late follicular phase. The coincidence of elevated GnRH-II gene expression during the preovulatory rise in circulating estradiol supports the hypothesis that estradiol exerts a positive feedback effect on GnRH-II but not GnRH-I. Moreover, the data give credence to the view that GnRH-II may be the primary GnRH form responsible for triggering the preovulatory LH surge in primates.

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