title: Organizational actions of postnatal estradiol in female sheep treated prenatally with testosterone: programming of prepubertal neuroendocrine function and the onset of puberty.
abstract: Prenatal testosterone (T) exposure defeminizes reproductive neuroendocrine function in female sheep, although the LH surge dysfunctions are initially less severe in gonadally intact females than in females subject to neonatal ovariectomy and estradiol (E) replacement. Because prepubertal ovarian production of E differs quantitatively and qualitatively from chronic E replacement, we tested the hypothesis that postnatal E exacerbates the consequences of prenatal T on the positive, but not the negative, steroid feedback controls of GnRH secretion. Our approach was to characterize prepubertal sensitivity to E negative feedback, the onset and maintenance of progestagenic cycles, and the LH surge response in ovary intact, prenatally untreated (control), and T-treated (T) sheep that were exposed postnatally to only endogenous E, or exposed to excess E by s.c. implant. Sensitivity to E negative feedback was reduced in T females, but excess postnatal E did not further increase LH pulse frequency. Excess E prevented ovarian cycles in several control females, and increased cycle irregularity in T females. However, the LH surge mechanism was functional in all control females (regardless of postnatal E exposure) and in some T females without excess E, but nonfunctional in T females with excess E. These findings suggest that postnatal E does not program increased resistance to E negative feedback, but excess postnatal E does disrupt other mechanisms required for ovarian cyclicity. We conclude that in this precocial species, prenatal steroids are sufficient to program controls of tonic LH secretion, but the LH surge mechanism is susceptible to further programming by postnatal E.
authors.affiliation: Reproductive Sciences Program, Department of Pediatrics, University of Michigan, 300 North Ingalls, Room 1111, Ann Arbor, Michigan 48109, USA. lmjackso@umich.edu
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Jackson
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Timmer
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Foster
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004353:Drug Evaluation, Preclinical; D047108:Embryonic Development / Q000187:drug effects* / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D030762:Estrous Cycle / Q000187:drug effects / Q000502:physiology; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology; D005260:Female; D007986:Luteinizing Hormone / Q000378:metabolism; D055099:Neuroendocrine Cells / Q000187:drug effects* / Q000502:physiology; D010052:Ovariectomy / Q000662:veterinary; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology; D011673:Pulsatile Flow / Q000187:drug effects; D012741:Sexual Maturation / Q000187:drug effects* / Q000502:physiology; D012756:Sheep; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone