Kisspeptin in the hypothalamus of two rat models of polycystic ovary syndrome

Abstract

Hyperandrogenism, disturbance of the hypothalamus-pituitary-ovary axis followed by elevated serum luteinizing hormone (LH) levels, and insulin resistance are involved in the complicated pathophysiology of polycystic ovary syndrome (PCOS). Kisspeptin is coexpressed with neurokinin B (NKB) in the arcuate nucleus (ARC), the center of the gonadotropin-releasing hormone pulse generator that is responsible for pulsatile LH secretion. We compared 2 androgenized rat models of PCOS to evaluate the estrous cycle, hormonal profiles, and expression of kisspeptin and NKB in the ARC. Rats in our postnatal dihydrotestosterone (DHT)-treatment model exhibited weight gain and persistent diestrus with normal LH levels. In contrast, irregular cycles, with elevated LH serum levels and normal body weight, were found in the prenatally DHT-treated rats. We also found increased signals of kisspeptin and NKB in the ARC of the prenatally DHT-treated rats, and not in the postnatally DHT-treated rats. Our results suggest that prenatal exposure to androgens may result in higher kisspeptin and NKB levels in the ARC, which could be associated with 1 phenotype of PCOS that is characterized by normal body weight and higher LH secretion, whereas in postnatally DHT-treated rats, characteristics such as weight gain and normal LH levels are seen in the obese PCOS phenotype.

Animal models of polycystic ovary syndrome: A review of hormone‐induced rodent models focused on hypothalamus‐pituitary‐ovary axis and neuropeptides

“…In postnatal DHT‐treated rats and mice, LH, FSH, E2, and T levels did not differ significantly from those in controls, although P4 was downregulated …”

“…Prenatal DHT‐treated diestrus rats had higher levels of LH and E2 and lower levels of P4; however, in mice the P4 levels were decreased whereas E2, T, and gonadotropin levels were unchanged relative to the control …”

“…Rats prenatally treated with DHT had fewer normal large, antral, preovulatory follicles and CLs, and more atretic cyst‐like follicles. Ovaries of prenatal DHT‐treated rats had a similar mass to those of control animals . In prenatal DHT‐treated mice, CL and antral follicle wall areas were decreased but the number of atretic cyst‐like follicles and thickness of the antral follicle theca cell layer were increased compared to control mice …”

“…Rats and mice prenatally administered DHT showed irregular cycles. The mice spent more days in diestrus and fewer in proestrus than controls, resulting in a decrease in the number of litters produced per 3 months …”

“…To generate prenatal DHT‐treated animals, mice were injected with 250 µg of DHT on days 16, 17, and 18 of gestation whereas rats were administered 3 mg of DHT daily from gestational day 16 to 19. The offspring served as prenatal DHT‐treated PCOS models …”