Endocrine Abstracts

Background: Polycystic ovarian syndrome (PCOS) is a common reproductive-endocrine disorder seen in women; characterized by increased GnRH pulsatility, hyperandrogenism, and cyst formation in ovary. GnRH release is controlled by higher centres of brain namely, hypothalamus and pituitary through various feedback mechanisms, one of them being neurotransmitters. However, no clear data is available with respect to GnRH regulation by neurotransmitters in PCOS. The aim of the present study was to evaluate status of neurotransmitters and their receptors in PCOS and to correlate this with GnRH pulsatility.

Materials and methods: PCOS was induced in rats using letrozole – an aromatase inhibitor – and validated for structural and metabolic characteristics of PCOS. Neurotransmitters were estimated from different regions of rat brain by HPLC and detected electrochemically. RNA was isolated from hypothalamus and pituitary using TRIzol reagent and cDNA was synthesized by first strand cDNA synthesis kit. This cDNA was further used for real-time expression studies of gonadotropins and neurotransmitter receptors.

Results: PCOS rats demonstrated increased hypothalamic GnRH1; pituitary GnRHR and LHβ mRNA levels as compared to control rats. Reduced levels of norepinephrine, dopamine, serotonin, γ-amino butyric acid, and epinephrine with increased glutamate levels were observed in pituitary and hypothalamus of PCOS rats as compared to control rats. Expression of neurotransmitter receptors – 5HT1A, GABAB1, D2R, and α1A receptor decreased while that of NMDA receptor increased in hypothalamus and pituitary of PCOS rats.

Conclusion: Letrozole treated rat demonstrated hormonal and metabolic characteristics of PCOS with peripheral cysts in the ovary. Present study confirms that modulation in GnRH stimulatory as well as inhibitory neurotransmitters could have contributed to increased GnRH pulsatility, further resulting into increased LH to FSH ratio in PCOS.