Kisspeptin in the Hypothalamus of 2 Rat Models of Polycystic Ovary Syndrome

Endocrinology. 2017 Feb 1;158(2):367-377. doi: 10.1210/en.2016-1333.


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.

MeSH terms

  • Animals
  • Arcuate Nucleus of Hypothalamus / metabolism*
  • Body Weight
  • Dihydrotestosterone
  • Disease Models, Animal
  • Estrous Cycle
  • Female
  • Gonadal Steroid Hormones / blood
  • Gonadotropins / blood
  • Hypothalamo-Hypophyseal System / metabolism
  • Hypothalamus, Anterior / metabolism
  • Kisspeptins / metabolism*
  • Ovary / metabolism
  • Ovary / pathology
  • Phenotype
  • Polycystic Ovary Syndrome / metabolism*
  • Polycystic Ovary Syndrome / pathology
  • Rats, Wistar


  • Gonadal Steroid Hormones
  • Gonadotropins
  • Kisspeptins
  • Dihydrotestosterone