Pivotal roles of α‐melanocyte‐stimulating hormone and the melanocortin 4 receptor in leptin stimulation of prolactin secretion in rats

Watanobe, Hajime; Schiöth, Helgi B.; Izumi, Junkichi

doi:10.1046/j.1471-4159.2003.01683.x

Cited by 13 publications

(8 citation statements)

References 66 publications

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“…It is possible that α-MSH acting at the pituitary level prevented the fall in pituitary prolactin content in the Tg-MSH mice. This would be consistent with the stimulatory effect of α-MSH on prolactin release reported in vitro in cultured lactotrophs[45]. However, given that basal and stress-induced prolactin release is suppressed in Tg-MSH mice, the effects of α-MSH on the dopaminergic regulation of prolactin appears to predominate.…”

Section: Discussionsupporting

confidence: 87%

“…This appears to be via stimulation of the MC3-R that is expressed by lactotrophs [25]. There is also a report that an α-MSH antiserum attenuates stimulation of prolactin by leptin [45]. Thus α-MSH may modulate prolactin release at both the pituitary and hypothalamic level.…”

Section: Discussionmentioning

confidence: 99%

“…There is also evidence of an anatomical connection between POMC and TIDA neurons as revealed by electron microscopy showing synaptic connections between POMC immunoreactive axon terminals and tyrosine hydroxylase-immunopositive cell bodies and dendrites [10]. However, in contrast at the pituitary level, there are some reports of stimulatory effects of α-MSH on prolactin including stimulation from cultured mouse pituitary cells [25, 45, 46]. …”

Section: Introductionmentioning

confidence: 99%

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Regulation of prolactin in mice with altered hypothalamic melanocortin activity

et al. 2012

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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.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulation of prolactin in mice with altered hypothalamic melanocortin activity

et al. 2012

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“…Previous reports indicated that HS024 diminishes proestrous and leptin-induced surges of LH and PRL [46, 47, 48, 49]. The mechanisms involved in the control of these surges are different from those involved in maintaining basal levels of PRL and LH.…”

Section: Discussionmentioning

confidence: 95%

Alpha-Melanocyte-Stimulating Hormone through Melanocortin-4 Receptor Inhibits Nitric Oxide Synthase and Cyclooxygenase Expression in the Hypothalamus of Male Rats

et al. 2004

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There is evidence that α-melanocyte-stimulating hormone (α-MSH) has immunomodulatory and anti-inflammatory actions within the brain. In this study, we tested whether these actions are due to inhibition of the synthesis of nitric oxide (NO) and prostaglandins induced by lipopolysaccharide (LPS). Since melanocortin subtype MC4 receptor has been detected in the hypothalamus, we investigated the effect of central administration of α-MSH and HS024 (a selective MC4 receptor antagonist) on the gene expression of inducible, neuronal and endothelial NO synthase (iNOS, nNOS and eNOS) and on cyclooxygenase (COX-1 and COX-2) expression in the mediobasal hypothalamus (MBH) of LPS-treated male Wistar rats. Peripheral administration of LPS (250 µg/rat, 3 h) induced iNOS and COX-2 gene expression in the MBH. This stimulatory effect was reduced by α-MSH (3 nmol/rat) injected 30 min before LPS. α-MSH and HS024 (1 nmol/rat) alone had no effect on iNOS and COX-2 expression. The action of α-MSH on LPS-induced iNOS and COX-2 mRNA levels was not observed in the presence of HS024, suggesting that MC4-R may be involved in the modulatory effect of α-MSH. None of these treatments produced any modifications in nNOS, eNOS and COX-1 expression in MBH. The increase in serum corticosterone levels induced by LPS was attenuated by α-MSH. Both LPS and α-MSH decreased serum LH and prolactin levels. HS024 failed to modify the inhibitory effects of LPS and α-MSH on prolactin release but reverted the effect of LPS on LH secretion, indicating that MC4-R activation may be involved in the effects of α-MSH on LH secretion in male rats. When we examined the in vitro effect of LPS (10 µg/ml) and LPS plus interferon-γ (IFN-γ, 100 ng/ml) on iNOS expression in MBH, an increase in iNOS mRNA levels was observed only in the presence of LPS + IFN-γ. This stimulatory effect was attenuated in the presence of α-MSH (5 µM), which by itself had no effect. No changes were found in nNOS, eNOS, COX-1 or COX-2 expression. These results indicate that α-MSH reduces the induction of iNOS and COX-2 gene expression at the hypothalamic level during endotoxemia and suggest that endogenous α-MSH may exert an inhibitory tone on iNOS and COX-2 transcription via MC4 receptors acting as a local anti-inflammatory agent within the hypothalamus.

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“…Serotonergic raphe neurons have been shown to lack the long isoform of leptin receptors (Ob-Rb) [7] and serotonin turnover was unaffected in several brain areas of normal rats after 3 days of intraperitoneal leptin infusion [8]. Basal and potassium-stimulated serotonin overflow were unaltered by the addition of leptin to synaptosomes or superfusion preparations of rat hypothalami [9,10].…”

Section: Introductionmentioning

confidence: 99%

Lateral hypothalamic serotonin is not stimulated during central leptin hypophagia

Telles

Silva

Watanabe

et al. 2013

Regulatory Peptides

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Whether leptin targets the hypothalamic serotonergic system to inhibit food intake is not established. We examined the effect of a short-term i.c.v. leptin treatment on serotonin microdialysate levels in rat lateral hypothalamus. Adipose tissue gene expression was also evaluated. Male rats received four daily injections of leptin (5 μg) or vehicle (with pair-feeding to leptin-induced intake) and a fifth injection during collection of LH microdialysates. We found that serotonin and 5-HIAA levels were not affected by the leptin pre-treatment, as basal levels were similar between the leptin and the pair-fed group. These levels remained unaltered after the acute leptin injection. For gene expression studies, rats were pre-treated with five daily injections of either leptin (5 μg) or vehicle (with either pair-feeding or ad libitum intake). mRNA levels of resistin, adiponectin, lipoprotein lipase, and PPAR-gamma were unaltered by either leptin or pair-feeding. Leptin gene expression was significantly reduced by leptin but not by pair-feeding, in both the retroperitoneal (-74%) and the epididymal (-99%) depots while no differences were observed in the subcutaneous depot. The observations confirmed the absence of an acute stimulatory effect of central leptin on serotonin release in the lateral hypothalamus and showed that the pre-treatment with leptin failed to modify this pattern. This indicates that components of the serotonergic system are probably not directly affected by leptin. Additionally, the central effect of leptin was able to downregulate its own adipose tissue gene expression in a depot-specific manner while other adipokine genes were not affected.

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Pivotal roles of α‐melanocyte‐stimulating hormone and the melanocortin 4 receptor in leptin stimulation of prolactin secretion in rats

Cited by 13 publications

References 66 publications

Regulation of prolactin in mice with altered hypothalamic melanocortin activity

Regulation of prolactin in mice with altered hypothalamic melanocortin activity

Alpha-Melanocyte-Stimulating Hormone through Melanocortin-4 Receptor Inhibits Nitric Oxide Synthase and Cyclooxygenase Expression in the Hypothalamus of Male Rats

Lateral hypothalamic serotonin is not stimulated during central leptin hypophagia

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