{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:16:09Z","timestamp":1759940169212},"reference-count":39,"publisher":"The Endocrine Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,5,1]]},"abstract":"<jats:p>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 sc 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.<\/jats:p>","DOI":"10.1210\/en.2008-1307","type":"journal-article","created":{"date-parts":[[2009,1,9]],"date-time":"2009-01-09T02:38:05Z","timestamp":1231468685000},"page":"2317-2324","source":"Crossref","is-referenced-by-count":8,"title":["Organizational Actions of Postnatal Estradiol in Female Sheep Treated Prenatally with Testosterone: Programming of Prepubertal Neuroendocrine Function and the Onset of Puberty"],"prefix":"10.1210","volume":"150","author":[{"given":"Leslie M.","family":"Jackson","sequence":"first","affiliation":[{"name":"Reproductive Sciences Program, Departments of Pediatrics (L.M.J., K.M.T.), University of Michigan, Ann Arbor, Michigan 48109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen M.","family":"Timmer","sequence":"first","affiliation":[{"name":"Reproductive Sciences Program, Departments of Pediatrics (L.M.J., K.M.T.), University of Michigan, Ann Arbor, Michigan 48109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas L.","family":"Foster","sequence":"first","affiliation":[{"name":"Departments of Obstetrics and Gynecology, (D.L.F.), University of Michigan, Ann Arbor, Michigan 48109"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2009,1,8]]},"reference":[{"key":"2020071612533551500_R1","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1126\/science.6163211","article-title":"Sexual Differentiation of the central nervous system.","volume":"211","author":"MacLusky","year":"1981","journal-title":"Science"},{"key":"2020071612533551500_R2","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1159\/000127010","article-title":"Prenatal testosterone differentially masculinizes tonic and surge modes of luteinizing hormone secretion in the developing sheep.","volume":"62","author":"Wood","year":"1995","journal-title":"Neuroendocrinology"},{"key":"2020071612533551500_R3","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1111\/j.1365-2826.1996.tb00698.x","article-title":"Sexual differentiation of the surge mode of gonadotropin secretion: prenatal androgens abolish the gonadotropin-releasing hormone surge in the sheep.","volume":"8","author":"Herbosa","year":"1996","journal-title":"J Neuroendocrinol"},{"key":"2020071612533551500_R4","first-page":"83","article-title":"Sexual differentiation of the neuroendocrine control of gonadotrophin secretion: concepts derived from sheep models.","volume":"59","author":"Foster","year":"2002","journal-title":"Reprod Suppl"},{"key":"2020071612533551500_R5","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1210\/en.2002-220965","article-title":"Prenatal programming of reproductive neuroendocrine function: fetal androgen exposure produces progressive disruption of reproductive cycles in sheep.","volume":"144","author":"Birch","year":"2003","journal-title":"Endocrinology"},{"key":"2020071612533551500_R6","doi-asserted-by":"crossref","first-page":"4281","DOI":"10.1210\/en.2005-0322","article-title":"Fetal programming: excess prenatal testosterone reduces postnatal luteinizing hormone, but not follicle-stimulating hormone, responsiveness to estradiol negative feedback in the female.","volume":"146","author":"Sarma","year":"2005","journal-title":"Endocrinology"},{"key":"2020071612533551500_R7","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1095\/biolreprod66.4.924","article-title":"Fetal programming: prenatal androgen disrupts positive feedback actions of estradiol but does not affect timing of puberty in female sheep.","volume":"66","author":"Sharma","year":"2002","journal-title":"Biol Reprod"},{"key":"2020071612533551500_R8","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1095\/biolreprod.107.065904","article-title":"Developmental programming: deficits in reproductive hormone dynamics and ovulatory outcomes in prenatal, testosterone-treated sheep.","volume":"78","author":"Veiga-Lopez","year":"2008","journal-title":"Biol Reprod"},{"key":"2020071612533551500_R9","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1210\/en.2005-1338","article-title":"Fetal programming: prenatal testosterone treatment leads to follicular persistence\/luteal defects; partial restoration of ovarian function by cyclic progesterone treatment.","volume":"147","author":"Manikkam","year":"2006","journal-title":"Endocrinology"},{"key":"2020071612533551500_R10","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1210\/endo-118-6-2225","article-title":"Control of gonadotropin secretion in the male during puberty: a decrease in response to steroid inhibitory feedback in the absence of an increase in steroid-independent drive in the sheep.","volume":"118","author":"Olster","year":"1986","journal-title":"Endocrinology"},{"key":"2020071612533551500_R11","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1095\/biolreprod45.3.471","article-title":"Patterns of circulating gonadotropins and ovarian steroids during the first periovulatory period in the developing sheep.","volume":"45","author":"Ryan","year":"1991","journal-title":"Biol Reprod"},{"key":"2020071612533551500_R12","doi-asserted-by":"crossref","first-page":"4200","DOI":"10.1210\/en.2007-1382","article-title":"Sexual differentiation of the external genitalia and the timing of puberty in the presence of an antiandrogen in sheep.","volume":"149","author":"Jackson","year":"2008","journal-title":"Endocrinology"},{"key":"2020071612533551500_R13","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1017\/S0021859600024874","article-title":"Subjective assessment of body fat in live sheep.","volume":"72","author":"Russel","year":"1969","journal-title":"J Agr Sci"},{"key":"2020071612533551500_R14","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1210\/endo-126-2-1206","article-title":"Sexual differentiation of the mechanism controlling pulsatile secretion of luteinizing hormone contributes to sexual differences in the timing of puberty in sheep.","volume":"126","author":"Claypool","year":"1990","journal-title":"Endocrinology"},{"key":"2020071612533551500_R15","first-page":"2127","author":"Foster","year":"2006"},{"key":"2020071612533551500_R16","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S0378-4320(03)00094-0","article-title":"Antral follicle growth and endocrine changes in prepubertal cattle, sheep and goats.","volume":"78","author":"Rawlings","year":"2003","journal-title":"Anim Reprod Sci"},{"key":"2020071612533551500_R17","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1210\/endo-97-4-985","article-title":"Sequential patterns of circulating luteinizing hormone in female sheep from early postnatal life through the first estrous cycles.","volume":"97","author":"Foster","year":"1975","journal-title":"Endocrinology"},{"key":"2020071612533551500_R18","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1095\/biolreprod37.4.755","article-title":"Changes in episodic luteinizing hormone secretion leading to puberty in the lamb.","volume":"37","author":"Huffman","year":"1987","journal-title":"Biol Reprod"},{"key":"2020071612533551500_R19","doi-asserted-by":"crossref","first-page":"5797","DOI":"10.1210\/endo.140.12.7205","article-title":"In utero exposure of female lambs to testosterone reduces the sensitivity of the gonadotropin-releasing hormone neuronal network to inhibition by progesterone.","volume":"140","author":"Robinson","year":"1999","journal-title":"Endocrinology"},{"key":"2020071612533551500_R20","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1210\/endo-115-3-1186","article-title":"Preovulatory gonadotropin surge system of prepubertal female sheep is exquisitely sensitive to the stimulatory feedback action of estradiol.","volume":"115","author":"Foster","year":"1984","journal-title":"Endocrinology"},{"key":"2020071612533551500_R21","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1210\/endo-101-3-807","article-title":"A new concept for control of the estrous cycle of the ewe based upon temporal relationships between luteinizing hormone, estradiol, and progesterone in peripheral serum and evidence that progesterone inhibits tonic LH secretion.","volume":"101","author":"Hauger","year":"1977","journal-title":"Endocrinology"},{"key":"2020071612533551500_R22","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1210\/endo-126-5-2719","article-title":"Metabolic interfaces between growth and reproduction. 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