title: Inhibitory roles of the mammalian GnIH ortholog RFRP3 in testicular activities in adult mice.
abstract: The aim of this study was to evaluate the effects of in vivo and in vitro treatments with RFamide-related peptide 3 (RFRP3), a mammalian gonadotropin-inhibitory hormone ortholog, on testicular activities, i.e. spermatogenesis and steroidogenesis, in mice. Mice were treated in vivo with different doses of RFRP3 (control: 0.02 μg, 0.2 μg, and 2.0 μg/day) for 8 days. For in vitro study, the testes of mice were evaluated with different doses of RFRP3 (control: 1 and 10 ng/ml) with or without LH (control: 10 and 100 ng/ml) for 24 h at 37 °C. RFRP3 treatment produced significant changes in the body mass, circulating steroid level, and testicular activity in mice. RFRP3 treatment also caused dose-dependent histological changes in spermatogenesis, such as decline in germ cell proliferation and survival markers and increase in apoptotic markers in testis. Both in vivo and in vitro studies showed the inhibitory effect of RFRP3 on testosterone synthesis in the testis. RFRP3 inhibited the expression of the receptor for LH (LHCGR), STAR protein, cytochrome P450 side-chain cleavage (CYP11A1) and 3β-hydroxysteroid dehydrogenase in the testis, and testosterone secretion dose dependently. This study also suggested that the inhibitory effect of RFRP3 in the testis may be mediated through local production of GnRH. Thus, RFRP3 inhibits testicular steroidogenesis and spermatogenesis either indirectly through GnRH or by directly influencing germ cell proliferation, survival, and apoptosis.
authors.affiliation: Department of ZoologyBanaras Hindu University, Varanasi 221 005, Uttar Pradesh, IndiaDepartment of BiologyWaseda University, Tokyo 162-8480, Japan.
authors.forename: Shabana
authors.initials: S
authors.lastname: Anjum
authors.affiliation: Department of ZoologyBanaras Hindu University, Varanasi 221 005, Uttar Pradesh, IndiaDepartment of BiologyWaseda University, Tokyo 162-8480, Japan akrishna_ak@yahoo.co.in.
authors.forename: Amitabh
authors.initials: A
authors.lastname: Krishna
authors.affiliation: Department of ZoologyBanaras Hindu University, Varanasi 221 005, Uttar Pradesh, IndiaDepartment of BiologyWaseda University, Tokyo 162-8480, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Tsutsui
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007150:Immunohistochemistry; D007986:Luteinizing Hormone / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D009479:Neuropeptides / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011974:Receptors, LH / Q000378:metabolism; D011966:Receptors, LHRH / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis* / Q000097:blood; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D009479:Neuropeptides; D010750:Phosphoproteins; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; C416987:RFamide peptide; D011974:Receptors, LH; D011966:Receptors, LHRH; D000098682:Steroidogenic Acute Regulatory Protein; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D015096:3-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3
keywords: RFamide-related peptide 3; gonadotropin-inhibitory hormone; mice; spermatogenesis; steroidogenesis; testis