title: Complete Sertoli cell proliferation induced by follicle-stimulating hormone (FSH) independently of luteinizing hormone activity: evidence from genetic models of isolated FSH action.
abstract: Defining the gonadal effects of FSH distinct from those of LH remains difficult. We have characterized and compared the level of Sertoli and germ cell development in three mouse models recently created to isolate FSH activity from LH effects. Two models used LH-deficient hypogonadal (hpg) mice to selectively study either pituitary-independent transgenic (tg) FSH or ligand-independent activated tg FSH receptor (FSHR(+)) expression, and the third model used LH receptor (LHR)-deficient mice to isolate and examine endogenous mouse FSH effects. Stereological evaluation revealed tg-FSH or tg-FSHR(+) activity significantly increased total Sertoli cell numbers per testis in both hpg models relative to control hpg testes. Furthermore, tg-FSH dose-dependently restored hpg Sertoli cells to wild-type (wt) (non-hpg) levels, and LHR-/- testes also exhibited wt Sertoli numbers. Spermatogonial proliferation and meiotic development were enhanced by tg-FSHR(+) or tg-FSH. Despite producing normal Sertoli numbers, isolated tg-FSH activity only increased total spermatogonia and spermatocyte populations to 57 and 44% of wt, which was comparable to spermatogonia and spermatocyte numbers observed in LHR-null testes (45 and 34% of wt). Selective FSH activity initiated round spermatid formation in all three models. However, elongated spermatid formation was detected in tg-FSH and tg-FSHR(+) hpg testes but not in LHR-/- testes, which may reflect even lower intratesticular testosterone levels in LHR-null compared with hpg testes. FSH increased round and elongated spermatid numbers in hpg testes to 16 and 6% of wt without altering intratesticular testosterone levels, but failed to produce spermatozoa demonstrating the inability of FSH to complete spermatogenesis. These findings revealed that full Sertoli cell proliferation can be accomplished by FSH activity without LH requirement, and although postnatal mitotic and meiotic germ cell development can be promoted by FSH alone, LH-mediated effects remain a critical determinant for initiating the full complement of germ cells and final stages of postmeiotic development.
authors.affiliation: Andrology Laboratory, ANZAC Research Institute, Concord Hospital, Sydney, Australia. charles@anzac.edu.au
authors.forename: Charles M
authors.initials: CM
authors.lastname: Allan
authors.forename: Alvaro
authors.initials: A
authors.lastname: Garcia
authors.forename: Jenny
authors.initials: J
authors.lastname: Spaliviero
authors.forename: Fu-Ping
authors.initials: FP
authors.lastname: Zhang
authors.forename: Mark
authors.initials: M
authors.lastname: Jimenez
authors.forename: Ilpo
authors.initials: I
authors.lastname: Huhtaniemi
authors.forename: David J
authors.initials: DJ
authors.lastname: Handelsman
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016922:Cellular Senescence; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000502:physiology*; D006728:Hormones / Q000097:blood; D006801:Humans; D007006:Hypogonadism / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008024:Ligands; D007986:Luteinizing Hormone / Q000172:deficiency*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D009929:Organ Size; D010902:Pituitary Gland / Q000503:physiopathology; D011962:Receptors, FSH / Q000378:metabolism; D012708:Sertoli Cells / Q000473:pathology*; D013094:Spermatozoa; D013737:Testis / Q000473:pathology
chemical_list: D006728:Hormones; D008024:Ligands; D011962:Receptors, FSH; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone