Frontiers in endocrinology · 2023
Suppression of neurotransmission on gonadotropin-releasing hormone neurons in letrozole-induced polycystic ovary syndrome: A mouse model.
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Bhattarai Pravin, Rijal Santosh, Bhattarai Janardhan P, Cho Dong Hyu, Han Seong Kyu
Аннотация
OBJECTIVE: Polycystic ovarian syndrome (PCOS) is a heterogeneous endocrine disorder in reproductive-age women, characterized by the accretion of small cystic follicles in the ovary associated with chronic anovulation and overproduction of androgens. Ovarian function in all mammals is controlled by gonadotropin-releasing hormone (GnRH) neurons, which are the central regulator of the hypothalamic-pituitary-gonadal (HPG) axis. However, the impact on the neurotransmitter system regulating GnRH neuronal function in the letrozole-induced PCOS mouse model remains unclear.
METHODS: In this study, we compared the response of various neurotransmitters and neurosteroids regulating GnRH neuronal activities between letrozole-induced PCOS and normal mice via electrophysiological techniques.
RESULTS: Response to neurotransmitter systems like GABAergic, glutamatergic and kisspeptinergic were suppressed in letrozole-fed compared to normal mice. In addition, neurosteroids tetrahydrodeoxycorticosterone (THDOC) and 4,5,6,7-tetrahydroisoxazolo[5,4-c] pyridine-3-ol (THIP) mediated response on GnRH neurons were significantly smaller on letrozole-fed mice compared to normal mice. Furthermore, we also found that letrozole-fed mice showed irregularity in the estrous cycle, increased body weight, and anovulation in female mice.
CONCLUSION: These findings suggest that PCOS is an endocrine disorder that may directly affect the neurotransmitter system regulating GnRH neuronal activity at the hypothalamic level and impact reproductive physiology.
METHODS: In this study, we compared the response of various neurotransmitters and neurosteroids regulating GnRH neuronal activities between letrozole-induced PCOS and normal mice via electrophysiological techniques.
RESULTS: Response to neurotransmitter systems like GABAergic, glutamatergic and kisspeptinergic were suppressed in letrozole-fed compared to normal mice. In addition, neurosteroids tetrahydrodeoxycorticosterone (THDOC) and 4,5,6,7-tetrahydroisoxazolo[5,4-c] pyridine-3-ol (THIP) mediated response on GnRH neurons were significantly smaller on letrozole-fed mice compared to normal mice. Furthermore, we also found that letrozole-fed mice showed irregularity in the estrous cycle, increased body weight, and anovulation in female mice.
CONCLUSION: These findings suggest that PCOS is an endocrine disorder that may directly affect the neurotransmitter system regulating GnRH neuronal activity at the hypothalamic level and impact reproductive physiology.