SINGLE NUCLEOTIDE GENE POLYMORPHISMS AND FUNCTIONAL HYPOTHALAMIC AMENORRHEA

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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. The objective of this Pilot project was to test the hypothesis that genetic variation in a novel gene termed EAP1 gene, manifested in the form of unique single nucleotide polymorphisms (SNPs), is a mechanism underlying the disorder of functional hypothalamic amenorrhea (FHA). The PI and his colleagues recently reported the functional characterization of this gene (termed EAP1, Enhanced at Puberty 1) and provided evidence supporting the concept that EAP1 is an upstream transcriptional regulator of neuronal networks controlling female reproductive function. These results also suggested that EAP1 plays an essential role in the control of female reproductive cyclicity. FHA is a disorder of the neuroendocrine brain that affects 3% of amenorrhea cases in women of reproductive age, and accounts for over 30% of all cases of amenorrhea. A natural nonhuman primate model of FHA exists in the ONPRC colony, with as many as 10% of adult females failing to cycle regularly or not cycling at all. The molecular underpinnings of this deficiency remain unknown, but they may be related to detrimental sequence defects in genes, such as EAP1, that control the rhythmic output of GnRH secretion from the hypothalamus. The results of this study, now completed, howed a significant association between a SNP located in the EAP1 promoter region and the incidence of amenorrhea in adult rhesus monkeys.