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Regulation by Estradiol of Hypothalamic Somatostatin Gene Expression: Possible Involvement of Somatostatin in the Control of Luteinizing Hormone Secretion in the Ewe

Unité Mixte de Recherche, Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique/Centre National de la Recherche Scientifique/Université François Rabelais de Tours, 37380 Nouzilly, France

In the ewe, the mediobasal hypothalamus (MBH) is the primary central site for estradiol to generate the preovulatory GnRH/LH surges and sexual behavior. This area contains numerous neurons expressing the estradiol receptor alpha, distributed in the ventromedial nucleus (VMN) and the infundibular nucleus (IN). A large proportion of these neurons express somatostatin, making this neuropeptide a potential candidate for transmission of the estradiol signal to the GnRH neurons located in the preoptic area. We tested this hypothesis using ovariectomized ewes that had been subjected to an artificial estrous cycle. In the first experiment, 22 h after progesterone removal, ewes received estradiol (treated ewes) or empty implants (control ewes) for 4 h and then were killed. Using in situ hybridization, we showed that this short estradiol treatment increased the somatostatin mRNA amount by about 50% in the VMN and 42% in the IN. In the second experiment, preovulatory estradiol signal was replaced by somatostatin intracerebroventricular (ICV) administration. This treatment abolished LH pulsatility and dramatically decreased the mean basal level of LH secretion while it did not affect the mean plasma GH concentration. We demonstrated that an increase in somatostatin mRNA occurs at the time of the negative feedback effect of estradiol on LH secretion during the early stage of the GnRH surge induction. As ICV somatostatin administration inhibits the pulsatile LH secretion by acting on the central nervous system, we suggest that somatostatin synthesized in the MBH could be involved in the estradiol negative feedback before the onset of the preovulatory surge.

¹ Correspondence: Gilles Bruneau, UMR 6175, INRA/CNRS/Université François Rabelais de Tours, 37380 Nouzilly, France. FAX: 33 247 42 77 43; bruneau{at}tours.inra.fr

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