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Station de Physiologie de la Reproduction des Mammifères Domestiques, Institut National de la Recherche Agronomique (A.C.), 37380 Nouzilly, France; and Reproductive Sciences Program, University of Michigan (F.J.K.), Ann Arbor, Michigan 48109; and the Laboratory of Neuroendocrinology, The Babraham Institute (A.H.), Cambridge, United Kingdom CB2 4AT
Address all correspondence and requests for reprints to: Dr. A. Caraty, Station de Physiologie de la Reproduction des Mammifères Domestiques, Institut National de la Recherche Agronomique, 37380 Nouzilly, France.
Although a neural site of action for estradiol in inducing a LH surge
via a surge of GnRH is now well established in sheep, the precise
target(s) for estrogen within the brain is unknown. To address this
issue, two experiments were conducted during the breeding season using
an artificial model of the follicular phase. In the first experiment,
bilateral 17ß-estradiol microimplants were positioned in either the
medial preoptic area (MPOA) or the mediobasal hypothalamus (MBH), and
LH secretion was monitored. An initial negative feedback inhibition of
LH secretion was observed in ewes that had estradiol microimplants
located in the MPOA (6 of 6 ewes) or caudal MBH in the vicinity of the
arcuate nucleus (4 of 4). In contrast, a normal LH surge was only found
in animals bearing estradiol microimplants in the MBH (5 of 10).
Detailed analysis of estradiol microimplant location with respect to
the estrogen receptor-
-immunoreactive cells of the hypothalamus
revealed that 4 of the 5 ewes exhibiting a LH surge had microimplants
located bilaterally within or adjacent to the area of estrogen
receptor-expressing cells of the ventromedial nucleus. Two of these
ewes exhibited a LH surge without showing any form of estrogen negative
feedback. In the second experiment, we used the technique of
hypophyseal portal blood collection to monitor GnRH secretion directly
at the time of the LH surge induced by estradiol delivered either
centrally or peripherally. Central estradiol implants induced the GnRH
surge. The duration and mean plasma concentration of GnRH during the
surge were not different between animals given peripheral or central
MBH estradiol implants. Cholesterol-filled MBH microimplants did not
evoke a GnRH surge.
We conclude that the ventromedial nucleus is the primary site of action for estradiol in stimulating the preovulatory GnRH surge of the ewe, whereas the MPOA and possibly the caudal MBH are sites at which estrogen can act to inhibit LH secretion. These data provide evidence for the sites within the ovine hypothalamus responsible for mediating the bimodal influence of estradiol on GnRH secretion and suggest that different, and possibly independent, neuronal cell populations are responsible for the negative and positive feedback actions of estradiol.
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M. Kinoshita, H. Tsukamura, S. Adachi, H. Matsui, Y. Uenoyama, K. Iwata, S. Yamada, K. Inoue, T. Ohtaki, H. Matsumoto, et al. Involvement of Central Metastin in the Regulation of Preovulatory Luteinizing Hormone Surge and Estrous Cyclicity in Female Rats Endocrinology, October 1, 2005; 146(10): 4431 - 4436. [Abstract] [Full Text] [PDF]
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C. J. Scott, I. J. Clarke, and A. J. Tilbrook Neuronal Inputs from the Hypothalamus and Brain Stem to the Medial Preoptic Area of the Ram: Neurochemical Correlates and Comparison to the Ewe Biol Reprod, April 1, 2003; 68(4): 1119 - 1133. [Abstract] [Full Text] [PDF]
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L. Dufourny and D. C. Skinner Progesterone Receptor, Estrogen Receptor {alpha}, and the Type II Glucocorticoid Receptor Are Coexpressed in the Same Neurons of the Ovine Preoptic Area and Arcuate Nucleus: A Triple Immunolabeling Study Biol Reprod, November 1, 2002; 67(5): 1605 - 1612. [Abstract] [Full Text] [PDF]
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S. Nagatani, Y. Zeng, D. H. Keisler, D. L. Foster, and C. A. Jaffe Leptin Regulates Pulsatile Luteinizing Hormone and Growth Hormone Secretion in the Sheep Endocrinology, November 1, 2000; 141(11): 3965 - 3975. [Abstract] [Full Text] [PDF]
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