title: Regulation of cyclic adenosine 3',5'- monophosphate signaling and pulsatile neurosecretion by Gi-coupled plasma membrane estrogen receptors in immortalized gonadotrophin-releasing hormone neurons.
abstract: Immortalized GnRH neurons (GT1-7) express receptors for estrogen [estrogen receptor-alpha and-13(ERa and ERI3)] and progesterone (progesterone receptor A) and exhibit positive immunostaining for both intracellular and plasma membrane ERs. Exposure of GT1-7 cells to picomolar estradiol concentrations for 5-60 min caused rapid, sustained,and dose-dependent inhibition of cAMP production. In contrast, treatment with nanomolar estradiol concentrations for 60 min increased cAMP production. The inhibitory and stimulatory actions of estradiol on cAMP formation were abolished by the ER antagonist, ICI 182,780. The estradiol-induced inhibition of cAMP production was prevented by treatment with pertussis toxin, consistent with coupling of the plasma membrane ER to an inhibitory G protein. Coimmunoprecipitation studies demonstrated an estradiol-regulated stimulatory interaction between ERa and G,3 that was prevented by the ER antagonist, ICI 182,780. Exposure of perifused GT1-7 cells and hypothalamic neurons to picomolar estradiol levels increased the GnRH peak interval, shortened peak duration, and increased peak amplitude. These findings indicate that occupancy of the plasma membrane-associated ERs expressed in GT1-7 neurons by physio-logical estradiol levels causes activation of a G, protein and modulates cAMP signaling and neuropeptide secretion.
authors.affiliation: Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4510, USA.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Navarro
authors.forename: Sheikh Abdul
authors.initials: SA
authors.lastname: Saeed
authors.forename: Cynthia
authors.initials: C
authors.lastname: Murdock
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Martinez-Fuentes
authors.forename: Krishan K
authors.initials: KK
authors.lastname: Arora
authors.forename: Lazar Z
authors.initials: LZ
authors.lastname: Krsmanovic
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Catt
mesh_terms: D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D017931:DNA Primers; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D007987:Gonadotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000196:embryology* / Q000502:physiology; D007150:Immunohistochemistry; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009900:Optic Nerve / Q000502:physiology; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014599:Uterus / Q000502:physiology
chemical_list: D017931:DNA Primers; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D000242:Cyclic AMP