NEUROENDOCRINE MEDIATION OF SOCIALLY INDUCED ANOVULATION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project was initiated in July 2005 to study the neuroendocrine mechanisms and genetic vulnerability responsible for socially induced anovulation or functional hypothalamic anovulation using a female rhesus monkey model. Females were either homozygous for the longer promoter allele (l/l) for the gene that encodes the serotonin reuptake transporter (n = 20) or carried at least one of the short promoter length variants (l/s or s/s; n = 20). During the current year, we completed the assessment of the metabolic phenotype of females with different SERT genotypes. Females carrying the s allele, have lower body weights despite similar heights; have lower body mass index scores and smaller sagittal abdominal diameters as indices of adiposity; and have lower circulating levels of leptin and insulin. Following the completion of these assessments, females were removed from their natal groups to form 8 small groups of 5 monkeys each to test the hypothesis that females with the s allele will be responsive to the consequences of social subordination. Groups were formed so that all females were homogenous for the SERT genotype. That is, four groups were comprised entirely of l/l females and four groups were comprised entirely of females with at least one s allele. Data supported this hypothesis, as females with the s allele showed more metabolic deficits upon becoming subordinate than l/l females. In addition, subordinate females showed more activity within the limbic-hypothalamic-pituitary-adrenal axis and this was exacerbated in s variants females. Genotype had little effect on these measures in females attaining high dominance status. Ongoing studies are testing the hypothesis that supplementation with the metabolic hormone leptin will rescue the reproductive deficits shown in subordinate females, particularly those with the s allele in the SERT gene.