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Sexually Dimorphic Expression of Corticotropin-Releasing Hormone-Binding Protein in the Mouse Pituitary

Neuroscience Graduate Program (D.B.S., A.F.S.), Mental Health Research Institute (D.B.S., S.J.M., A.F.S.), and Department of Biological Chemistry (S.J.M., A.F.S.), University of Michigan, Ann Arbor Michigan 48109-0720

Address all correspondence and requests for reprints to: Dr. Audrey Seasholtz, Mental Health Research Institute, 205 Zina Pitcher Place, Ann Arbor, Michigan 48109-0720. E-mail: aseashol{at}umich.edu.

In the pituitary, CRH-binding protein (CRH-BP) neutralizes the ACTH-releasing activity of CRH. Because sexual dimorphisms exist at multiple levels of the hypothalamic-pituitary-adrenal axis, these studies examined expression of pituitary CRH-BP in the male and female mouse pituitary. Ribonuclease protection assays and ¹²⁵I-CRH cross-linking assays demonstrate greater expression of pituitary CRH-BP in female than male mice. Normalized CRH-BP mRNA levels in female mice are 2.58 times greater at proestrus than diestrus. Ovariectomy reduces pituitary CRH-BP mRNA levels to 11% of sham-ovariectomy control levels, and estradiol benzoate treatment restores CRH-BP mRNA to control levels. These data suggest that estrogen positively regulates pituitary CRH-BP. Dual in situ hybridization analysis reveals that CRH-BP expression increases significantly in proopiomelanocortin-expressing cells at proestrus, compared with metestrus (P = 0.003), suggesting that CRH-BP expression is estrogen regulated in corticotropes. Further studies reveal that approximately 80% of the CRH-BP transcripts in the proestrus mouse pituitary localize to prolactin-expressing cells, a novel site for CRH-BP expression. CRH-BP mRNA levels increase significantly at proestrus, compared with metestrus in prolactin-positive cells (P < 0.0001). This robust, estrogen-regulated expression of CRH-BP in lactotropes in female mice suggests that the pituitary is an important site for interactions between the hypothalamic-pituitary-adrenal axis and other endocrine systems.

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