Prenatal exposure of the ovine fetus to androgens reduces the proportion of neurons in the ventromedial and arcuate nucleus that are activated by short-term exposure to estrogen

Robinson, J.E. , Grindrod, J., Jeurissen, S., Taylor, J.A. and Unsworth, W.P. (2010) Prenatal exposure of the ovine fetus to androgens reduces the proportion of neurons in the ventromedial and arcuate nucleus that are activated by short-term exposure to estrogen. Biology of Reproduction, 82(1), pp. 163-170. (doi: 10.1095/biolreprod.109.079004) (PMID:19741207)

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Abstract

In sheep, the steroid control of gonadotropin-releasing hormone ( GNRH) release is sexually differentiated such that estrogen can trigger a GNRH surge and attendant reproductive behaviors in the female, but not the male. Furthermore, female lambs that have been exposed to testosterone during a critical window of in utero development are also unable to generate a GNRH surge. This study tests the hypothesis that exposure of the ovine fetus to androgens alters the development of key steroidreceptive neuronal inputs to the GNRH neurons. In adulthood, this results in reduced activation of specific neurons by estrogen in the male and testosterone-treated female. To make this determination, groups of ewes, rams, and testosterone-exposed ewes were treated with estrogen, and the activation of neurons in the mediobasal hypothalamus and brain stem determined by immunocytochemistry. A lower percentage of neurons in the ventrolateral aspect of the ventromedial nucleus (vlVMN) and the caudal arcuate nucleus (cARC), but not the brainstem, was activated by a 6-h exposure to estrogen in the androgenized and male animals. In the vlVMN, some of these neurons contain somatostatin; however, the phenotype of activated neurons in the cARC remains unknown. These data suggest that specific neural populations in these brain regions are involved in the estrogen feedback control of GNRH release in the sheep, and that the defeminization of the surge-generating system by in utero androgen exposure results, in part, from a failure of estrogen to activate key neural phenotypes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Robinson, Dr Jane
Authors: Robinson, J.E., Grindrod, J., Jeurissen, S., Taylor, J.A., and Unsworth, W.P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:Biology of Reproduction
ISSN:0006-3363
ISSN (Online):1529-7268
Published Online:09 September 2009

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
404241Prenatal programming of the reproductive axis - the role of somatostatinJane RobinsonBiotechnology and Biological Sciences Research Council (BBSRC)BB/D002214/1Institute of Biodiversity Animal Health and Comparative Medicine