Regulation of prolactin in mice with altered hypothalamic melanocortin activity

Abstract

This study used two mouse models with genetic manipulation of the melanocortin system to investigate prolactin regulation. Mice with overexpression of the melanocortin receptor (MC-R) agonist, α-melanocyte-stimulating hormone (Tg-MSH) or deletion of the MC-R antagonist agouti-related protein (AgRP KO) were studied. Male Tg-MSH mice had lower blood prolactin levels at baseline (2.9±0.3 vs 4.7±0.7 ng/ml) and after restraint stress(68 ±6.5 vs 117±22 ng/ml) versus WT (p<0.05); however, pituitary prolactin content was not different. Blood prolactin was also decreased in male AgRP KO mice at baseline (4.2±0.5 vs 7.6±1.3 ng/ml) and after stress (60±4.5 vs 86.1±5.7 ng/ml) vs WT (p <0.001). Pituitary prolactin content was lower in male AgRP KO mice (4.3±0.3 vs 6.7±0.5 μg/pituitary, p <0.001) versus WT. No differences in blood or pituitary prolactin levels were observed in female AgRP KO mice versus WT. Hypothalamic dopamine activity was assessed as the potential mechanism responsible for changes in prolactin levels. Hypothalamic tyrosine hydroxylase mRNA was measured in both genetic models versus WT mice and hypothalamic dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) content were measured in male AgRP KO and WT mice but neither were significantly different. However, these results do not preclude changes in dopamine activity as dopamine turnover was not directly investigated. This is the first study to show that baseline and stress-induced prolactin release and pituitary prolactin content are reduced in mice with genetic alterations of the melanocortin system and suggests that changes in hypothalamic melanocortin activity may be reflected in measurements of serum prolactin levels.

Meningeal CGRP‐Prolactin Interaction Evokes Female‐Specific Migraine Behavior

“…In contrast, we observed a transient allodynia in males with significant facial hypersensitivity only at 3 h following PRL application. Next, since 5 μg PRL likely causes tissue concentrations that are higher than those found under physiological and pathological conditions, 21,22 we applied a lower dose of PRL (0.5 μg) to the dura to determine whether this dose caused responses only in females. This lower PRL dose caused facial hypersensitivity in females (Fig 1B), lasting out to at least 7 days, while no effect was observed in males (Fig 1E).…”

Biphasic Effect of Melanocortin Agonists on Metabolic Rate and Body Temperature

“…Of seven candidate regions, only the arcuate nucleus showed increased Fos staining after MTII treatment in TH-immunoreactive neurons (Figure 7). Since melanocortins can act via arcuate dopaminergic neurons to suppress prolactin secretion (Dutia et al, 2012), we measured Fos activation in Mc3r−/−;Mc4r−/− mice, which presumably lack this function. In Mc3r−/−;Mc4r−/− mice treated with MTII, the percentage of TH-immunoreactive neurons that stained for Fos, while reduced compared to wild type mice, was significantly greater than in vehicle-treated Mc3r−/−;Mc4r−/− mice (Figure 7).…”

Morphological and Functional Changes of Pituitary GH and PRL Cells Following Prolonged Exposure of Female Rats to Constant Light

“…There is also evidence that corticotropin-releasing hormone serves as the mediator of the stress-induced suppression of GH via direct synaptic connections between somatostatin neurons (6). Many hypothalamic substances are implicated in the prolactin-secretory stress response, and besides dopamine they include serotonin, histamine, N-methyl-D,L-aspartic acid, atrial natriuretic peptide, b-endorphin and dynorphin, oxytocin, vasopressin (10) and melanocortins (50).…”