Background: Polycystic ovary syndrome (PCOS) is a frequent endocrine and metabolic disorder and the most common cause of infertility occurring in 510% of women of reproductive age. The characteristic endocrine abnormalities of PCOS involve hypersecretion of androgens and LH (as a consequence of increased GnRH frequency). Although PCOS signs generally become obvious at puberty, clinical and experimental evidence suggests an intrauterine origin for the syndrome. On the other hand, kisspeptin antagonists have been shown to reduce LH pulse frequency and amplitude.
Methods: RNAs were extracted from hypothalamus of prenatally androgenized (PNA) (n=18) and non-PNA female rats (n=14) thought estrus cycle. The ability of prenatal administration of kisspeptin antagonist P271, to alter GnRH mRNA expression and gonadotropin and steroid hormone levels, was tested using Cyber-green Real-time PCR and ELISA methods, respectively.
Results: Hypothalamic GnRH mRNA levels fluctuated in a cyclic-dependent manner, with a robust increase in the afternoon of proestrus phase. P271 treated animals showed reduced GnRH expression and gonadal steroid and gonadotropin levels.
Conclusion: PNA animals had increased GnRH mRNA expression and LH levels in diestrous phase than controls, which reduced in response to prenatally administered P271. This pilot study, for the first time, shows that prenatal intervention by P271 reduce LH pulsatility and T levels associated with PCOS.
Keywords: Kisspetin, P271, Gene Expression, Prenatal androgenisation
20 - 23 May 2017
European Society of Endocrinology