title: Androgen receptors in gonadotrophs in pituitary cultures from adult male monkeys and rats.
abstract: There is substantial evidence demonstrating that the principal feedback action of androgens to decrease LH secretion in male primates, including man, is to slow the GnRH pulse generator, whereas in male rats androgens not only decrease GnRH but also suppress LH synthesis and secretion through a direct pituitary effect. Previous experiments in our laboratory revealed that testosterone (T) suppresses LH secretion and decreases alpha-subunit mRNA levels in male rat pituitary cell cultures perifused with pulses of GnRH but not in pituitary cells from adult male monkeys. In the present study, we sought to determine whether the lack of responsiveness of gonadotrophs to androgens in the primate is androgen receptor (AR) related. Primary cultures were prepared from the anterior pituitary glands of adult male monkeys and rats. Cells were identified as gonadotrophs if they were immunoreactive for LH-beta or FSH-beta. Of these cells in the monkey, 80% contained both gonadotropins, 17% contained only LH-beta, and 3% contained only FSH-beta. AR immunoreactivity (IR) was nuclear in 22% and 15%, respectively, of monkey and rat FSH-beta-positive cells in the absence of T. Following T treatment, nuclear AR IR was identified in 79% of monkey and 81% of rat gonadotrophs. T treatment similarly intensified AR IR in mouse gonadotroph alphaT3-1 and LbetaT2 cells and in monkey and rat fibroblasts. Single-cell RT-PCR confirmed coexpression of LH-beta and AR mRNA as well as LH-beta and GH mRNA in monkey gonadotrophs. Our data reveal that most monkey, as well as rat, gonadotrophs are AR-positive with nuclear localization in the presence of T. GH expression is not required for AR expression in gonadotrophs. We conclude that the failure of T to inhibit LH secretion and decrease alpha-subunit mRNA expression in the male primate is not due a disturbance in AR nuclear shuttling.
authors.affiliation: Division of Endocrinology and Metabolism, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Okada
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fujii
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Moore
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Winters
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D037201:Follicle Stimulating Hormone, beta Subunit / Q000032:analysis*; D015870:Gene Expression; D013006:Growth Hormone / Q000235:genetics; D007124:Immunoenzyme Techniques; D007986:Luteinizing Hormone / Q000378:metabolism; D037101:Luteinizing Hormone, beta Subunit / Q000032:analysis* / Q000235:genetics; D008253:Macaca mulatta; D008297:Male; D010903:Pituitary Gland, Anterior / Q000737:chemistry* / Q000187:drug effects / Q000648:ultrastructure; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000494:pharmacology
chemical_list: D037201:Follicle Stimulating Hormone, beta Subunit; D037101:Luteinizing Hormone, beta Subunit; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013739:Testosterone; D007986:Luteinizing Hormone; D013006:Growth Hormone