title: A role for hypothalamic astrocytes in dehydroepiandrosterone and estradiol regulation of gonadotropin-releasing hormone (GnRH) release by GnRH neurons.
abstract: Molecules of astrocyte origin influence gonadotropin-releasing hormone (GnRH) release and GnRH neuronal growth and differentiation. Furthermore, type 1 astrocytes express steroid receptors, presenting the possibility that steroid actions on GnRH neurons might occur via astrocytes. Utilizing GT1-7 cells, a GnRH-secreting cell line, the present study demonstrates that astrocytes mediate dehydroepiandrosterone (DHEA) or estradiol (E2) stimulated GnRH secretion. Conditioned media (CM) from astrocytes cultured for 48 h alone, with DHEA (DHEA-CM), or with E2 (E2-CM) were collected, treated with charcoal to remove steroids, and added to GT1-7 cells in culture for 12 h to test the effect on GnRH secretion. DHEA-CM and E2-CM stimulated GnRH secretion by GT1-7 cells by 4- and 3-fold, respectively. The effect of DHEA-CM on GnRH secretion by GT1-7 cells appears to be related to both DHEA and its metabolite, E2, since blocking the metabolism of DHEA into estrogen in the DHEA-treated astrocytes partially reversed the stimulatory effect of DHEA-CM. Addition of transforming growth factor (TGF)-beta1-neutralizing antibody to the astrocyte cultures reversed the stimulatory effects of both DHEA-CM and E2-CM on GnRH secretion by GT1-7 cells, suggesting that TGF-beta1 derived from astrocytes may be the principle mediator of E2 and DHEA effects. These data provide evidence for a novel mechanism by which circulating steroids and/or neurosteroids may modulate GnRH secretion.
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, La Jolla, CA, USA. ismail.zwain@ferring.com
authors.forename: Ismail H
authors.initials: IH
authors.lastname: Zwain
authors.forename: Armando
authors.initials: A
authors.lastname: Arroyo
authors.forename: Paula
authors.initials: P
authors.lastname: Amato
authors.forename: Samuel S C
authors.initials: SS
authors.lastname: Yen
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001141:Aromatase / Q000235:genetics / Q000502:physiology; D001253:Astrocytes / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D015870:Gene Expression; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D051381:Rats; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000276:immunology; D053773:Transforming Growth Factor beta1
chemical_list: D000906:Antibodies; D017077:Culture Media, Conditioned; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D016376:Oligonucleotides, Antisense; D011960:Receptors, Estrogen; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007987:Gonadotropin-Releasing Hormone; D003687:Dehydroepiandrosterone; D004958:Estradiol; D001141:Aromatase