title: Low levels of Gαs and Ric8b in testicular sertoli cells may underlie restricted FSH action during infancy in primates.
abstract: FSH acts via testicular Sertoli cells (Sc) bearing FSH receptor (FSH-R) for regulating male fertility. Despite an adult-like FSH milieu in infant boys and monkeys, spermatogenesis is not initiated until the onset of puberty. We used infant and pubertal monkey Sc to reveal the molecular basis underlying developmental differences of FSH-R signaling in them. Unlike pubertal Sc, increasing doses of FSH failed to augment cAMP production by infant Sc. The expression of Gαs subunit and Ric8b, which collectively activate adenylyl cyclase (AC) for augmenting cAMP production and gene transcription, were significantly low in infant Sc. However, forskolin, which acts directly on AC bypassing FSH-R, augmented cAMP production and gene transcription uniformly in both infant and pubertal Sc. FSH-induced Gαs mRNA expression was higher in pubertal Sc. However, Gαi-2 expression was down-regulated by FSH in pubertal Sc, unlike infant Sc. FSH failed, but forskolin or 8-Bromoadenosine 3',5'-cyclic monophosphate treatment to infant Sc significantly augmented the expression of transferrin, androgen binding protein, inhibin-β-B, stem cell factor, and glial-derived neurotropic factor, which are usually up-regulated by FSH in pubertal Sc during spermatogenic onset. This suggested that lack of FSH mediated down-regulation of Gαi-2 expression and limited expression of Gαs subunit as well as Ric8b may underlie limited FSH responsiveness of Sc during infancy. This study also divulged that intracellular signaling events downstream of FSH-R are in place and can be activated exogenously in infant Sc. Additionally, this information may help in the proper diagnosis and treatment of infertile individuals having abnormal G protein-coupled FSH-R.
authors.affiliation: Cellular Endocrinology Laboratory (I.B., S.B., K.S., M.G., B.S.P., H.S., Y.S.D., S.S.M.) and Primate Research Centre (P.N., S.S.M.), National Institute of Immunology, New Delhi, India 110067.
authors.forename: Indrashis
authors.initials: I
authors.lastname: Bhattacharya
authors.forename: Sayon
authors.initials: S
authors.lastname: Basu
authors.forename: Kanchan
authors.initials: K
authors.lastname: Sarda
authors.forename: Mukkesh
authors.initials: M
authors.lastname: Gautam
authors.forename: Perumal
authors.initials: P
authors.lastname: Nagarajan
authors.forename: Bhola Shankar
authors.initials: BS
authors.lastname: Pradhan
authors.forename: Hironmoy
authors.initials: H
authors.lastname: Sarkar
authors.forename: Yendrembam Sangeeta
authors.initials: YS
authors.lastname: Devi
authors.forename: Subeer S
authors.initials: SS
authors.lastname: Majumdar
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D008253:Macaca mulatta / Q000254:growth & development* / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D012708:Sertoli Cells / Q000502:physiology*; D012741:Sexual Maturation; D015398:Signal Transduction
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs