Kisspeptin regulates prolactin release through hypothalamic dopaminergic neurons.
Szawka. Raphael E RE; Ribeiro. Aline B AB; Leite. Cristiane M CM; Helena. Cleyde V V CV; Franci. Celso R CR; Anderson. Greg M GM; Hoffman. Gloria E GE; Anselmo-Franci. Janete A JA
Key Findings
- Kisspeptin‑10 raises prolactin levels in estrogen‑treated female rats and in males, but not in estrogen‑deficient females
- The prolactin increase is linked to reduced activity (Fos expression) of hypothalamic dopamine neurons
- Kisspeptin‑10 does not stimulate prolactin release from isolated pituitary cells, indicating a central (brain) mechanism
Practical Outcomes
- If you’re considering kisspeptin supplements to influence reproductive hormones, be aware it might raise prolactin, especially when estrogen levels are high, which could affect fertility or cause side effects like reduced libido. Since the study used direct brain injection, the effect of oral or peripheral kisspeptin in humans is uncertain, so monitor prolactin if you experiment with it.
Summary
In rats, giving kisspeptin‑10 directly into the brain boosts the hormone prolactin, but only when estrogen is present. It does this by quieting dopamine‑producing neurons that normally keep prolactin low. The peptide doesn’t act directly on the pituitary gland itself.
Abstract
Prolactin (PRL) is tonically inhibited by dopamine (DA) released from neurons in the arcuate and periventricular nuclei. Kisspeptin plays a pivotal role in LH regulation. In rodents, kisspeptin neurons are found mostly in the anteroventral periventricular and arcuate nuclei, but the physiology of arcuate kisspeptin neurons is not completely understood. We investigated the role of kisspeptin in the control of hypothalamic DA and pituitary PRL secretion in adult rats. Intracerebroventricular kisspeptin-10 (Kp-10) elicited PRL release in a dose-dependent manner in estradiol (E2)-treated ovariectomized rats (OVX+E2), whereas no effect was found in oil-treated ovariectomized rats (OVX). Kp-10 increased PRL release in males and proestrous but not diestrous females. Associated with the increase in PRL release, intracerebroventricular Kp-10 reduced Fos-related antigen expression in tyrosine hydroxylase-immunoreactive (ir) neurons of arcuate and periventricular nuclei in OVX+E2 rats, with no effect in OVX rats. Kp-10 also decreased 3,4-dihydroxyphenylacetic acid concentration and 3,4-dihydroxyphenylacetic acid-DA ratio in the median eminence but not striatum in OVX+E2 rats. Double-label immunofluorescence combined with confocal microscopy revealed kisspeptin-ir fibers in close apposition to and in contact with tyrosine hydroxylase-ir perikarya in the arcuate. In addition, Kp-10 was not found to alter PRL release from anterior pituitary cell cultures regardless of E2 treatment. We provide herein evidence that kisspeptin regulates PRL release through inhibition of hypothalamic dopaminergic neurons, and that this mechanism is E2 dependent in females. These findings suggest a new role for central kisspeptin with possible implications for reproductive physiology.
Study Information
pubmed
2010
2010-04-21T00:00:00.000Z
10.1210/en.2009-1414
96
64