Kisspeptin Stimulation of Prolactin Secretion Requires Kiss1 Receptor but Not in Tuberoinfundibular Dopaminergic Neurons

Endocrinology. 2019 Mar 1;160(3):522-533. doi: 10.1210/en.2018-00932.


Kisspeptin has been shown to stimulate prolactin secretion. We investigated whether kisspeptin acts through the Kiss1 receptor (Kiss1r) to regulate dopamine and prolactin. Initially, we evaluated prolactin response in a Kiss1r-deficient mouse line, in which Kiss1r had been knocked into GnRH neurons (Kiss1r-/-R). Intracerebroventricular kisspeptin-10 (Kp-10) increased prolactin release in wild-type but not in Kiss1r-/-R female mice. In ovariectomized, estradiol-treated rats, the Kiss1r antagonist kisspeptin-234 abolished the Kp-10-induced increase in prolactin release but failed to prevent the concomitant reduction in the activity of tuberoinfundibular dopaminergic (TIDA) neurons, as determined by the 3,4-dihydroxyphenylacetic acid/dopamine ratio in the median eminence. Using whole-cell patch clamp recordings in juvenile male rats, we found no direct effect of Kp-10 on the electrical activity of TIDA neurons. In addition, dual-label in situ hybridization in the hypothalamus of female rats showed that Kiss1r is expressed in the periventricular nucleus of the hypothalamus (Pe) and arcuate nucleus of the hypothalamus (ARC) but not in tyrosine hydroxylase (Th)-expressing neurons. Kisspeptin also has affinity for the neuropeptide FF receptor 1 (Npffr1), which was expressed in the majority of Pe dopaminergic neurons but only in a low proportion of TIDA neurons in the ARC. Our findings demonstrate that Kiss1r is necessary to the effect of kisspeptin on prolactin secretion, although TIDA neurons lack Kiss1r and are electrically unresponsive to kisspeptin. Thus, kisspeptin is likely to stimulate prolactin secretion via Kiss1r in nondopaminergic neurons, whereas the colocalization of Npffr1 and Th suggests that Pe dopaminergic neurons may play a role in the kisspeptin-induced inhibition of dopamine release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine / metabolism*
  • Dopaminergic Neurons / physiology
  • Female
  • Kisspeptins / metabolism*
  • Male
  • Mice, Knockout
  • Paraventricular Hypothalamic Nucleus / metabolism*
  • Prolactin / metabolism*
  • Rats, Wistar
  • Receptors, Kisspeptin-1 / metabolism*
  • Receptors, Neuropeptide / metabolism
  • Tyrosine 3-Monooxygenase / metabolism


  • Kisspeptins
  • Receptors, Kisspeptin-1
  • Receptors, Neuropeptide
  • neuropeptide FF receptor
  • Prolactin
  • Tyrosine 3-Monooxygenase
  • Dopamine