Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2015) 37 EP696 | DOI: 10.1530/endoabs.37.EP696

ECE2015 Eposter Presentations Pituitary: basic and neuroendocrinology (62 abstracts)

Unravelling the role of stress regulators on GnRH release in Letrozole induced PCOS rat model

Nirja Chaudhari & Laxmipriya Nampoothiri


Department of Biochemistry, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India


Background and aim: polycystic ovarian syndrome is a multi aetiological female endocrinopathy wherein one of the major target organs affected is adrenal. It is important to note that adrenal plays key role in evoking stress mediated responses in brain; which can in turn affect GnRH, the main regulator of HPG axis. Along with corticotrophin releasing factor (CRF), newly discovered neuropeptides- urocortin2 and RF-amide related peptide-3 (RFRP-3) (mammalian GnIH analogue) are also known to modulate stress. However, complex regulation of GnRH axis via stress regulatory molecules and gonadal function adaptations is not clear. Thereby, current study was undertaken to elucidate the interaction of stress regulators with GnRH in PCOS pathology.

Material and methods: PCOS was induced in rat using letrozole-an aromatase inhibitor and confirmed for pathology. Hormones-gonadotropins, androgen, oestradiol, progesterone levels were measured by ELISA. Regulatory neurotransmitter-GABA was estimated by HPLC. Expression studies of GnRH regulatory neuropetides and their receptors- CRF1, CRFR1, Ucn2, CRFR2, GnRH, GnRHR, RFRP-3, GPR-147 were carried out using real-time PCR.

Results: Hypothalamus and pituitary of PCOS rats demonstrated an increase in corticosterone (P<0.01) and androgen levels (P<0.01) whereas progesterone (P<0.05) and estradiol (P<0.01) levels were decreased. These altered levels of steroids were parallel to changes obtained in their receptors (GR, AR, ER-α, ER-β, PR). GABA levels were significantly decreased in hypothalamus (P<0.01) and pituitary (P<0.05) with reduced GABAB1 receptor expression in PCOS rats. PCOS rats also showed significant alterations in mRNA expressions of Ucn2, RFRP-3 and GnRH1 with their receptors CRF2, GPR-147 and GnRHR, respectively.

Conclusion: This study elucidates the complex regulation of GnRH in the hypothalamus and pituitary by stress elements- Ucn2, RFRP-3 and their involvement in altered GnRH release in PCOS pathology.

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