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Effects of Sex Steroids on Secretory Granule Formation in Gonadotropes of Castrated Male Rats with Respect to Granin Expression¹

Department of Cell Biology and Anatomy I (T.W., Y.O., S.W., Y.U.), Osaka University Medical School, 565 Osaka; and the Doctoral Program in Medical Sciences (T.B.), University of Tsukuba, 305 Tsukuba, Japan; and the Department of Anatomy I (T.J., D.G.), Hannover Medical School, D-30625 Hannover, Germany

Address all correspondence and requests for reprints to: Dr. Tsuyoshi Watanabe, Department of Cell Biology and Anatomy I, Osaka University Medical School, Yamadaoka 2–2, Suita-shi, 565 Osaka, Japan. E-mail: tyshwata{at}anat1.med.osaka-u.ac.jp

Pituitary gonadotropes show sex-related differences in their ultrastructure. Typical gonadotropes of male rats exhibit both large granules, which contain chromogranin A (CgA), and small granules, which contain secretogranin II (SgII). In contrast, typical female rat gonadotropes show only a very few large granules among the numerous small granules. To clarify the nature of the biogenesis of these secretory granules and the effects of sex steroids, the ultrastructural and immunocytochemical changes in gonadotropes were examined in castrated male rats supplied with a testosterone or estradiol implant. In castrated rats, pituitary expression and plasma levels of LH increased drastically, but the pituitary content of CgA decreased. The majority of gonadotropes then showed features of "castration cells" containing many small secretory granules. A testosterone implant to castrated rats remarkably suppressed the expression and circulating levels of LH and increased the CgA content in the pituitary to near-normal levels. In this situation, immunocytochemical studies demonstrated that gonadotropes again exhibited large and small secretory granules with the respective localization of CgA and SgII. On the contrary, in castrated rats supplied with an estradiol implant, the expression and content of CgA in the pituitary were remarkably suppressed, and large secretory granules disappeared from gonadotropes. These results suggest that the expression of CgA in gonadotropes is regulated differently by male and female sex steroids. These different effects of androgen and estrogen on the expression level of CgA are closely associated with the sex-related differences in the ultrastructure of secretory granules within gonadotropes.

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