Regulation of prolactin in mice with altered hypothalamic melanocortin activity.

Regulation of prolactin in mice with altered hypothalamic melanocortin activity.
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DOI:
10.1016/j.peptides.2012.07.006
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发表时间:
2012-09
期刊:
影响因子:
3
通讯作者:
Wardlaw SL
Wardlaw SL
中科院分区:
医学3区
文献类型:
--
作者:
Dutia R;Kim AJ;Mosharov E;Savontaus E;Chua SC Jr;Wardlaw SL

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本研究使用了两个小鼠模型与黑皮质素系统的遗传操作,以调查催乳素的调节。研究了黑皮质素受体(MC-R)激动剂、α-黑素细胞刺激激素(Tg-MSH)过表达或MC-R拮抗剂刺豚鼠相关蛋白(AgRP KO)缺失的小鼠。与WT相比,雄性Tg-MSH小鼠在基线(2.9±0.3 vs 4.7±0.7 ng/ml)和束缚应激后(68 ±6.5 vs 117±22 ng/ml)的血液催乳素水平较低(p<0.05);然而,垂体催乳素含量没有差异。与WT相比,雄性AgRP KO小鼠在基线(4.2±0.5 vs 7.6±1.3 ng/ml)和应激后(60±4.5 vs 86.1±5.7 ng/ml)的血催乳素也降低(p <0.001)。与WT相比,雄性AgRP KO小鼠的垂体泌乳素含量较低(4.3±0.3 vs 6.7±0.5 μg/垂体,p <0.001)。与WT相比,在雌性AgRP KO小鼠中未观察到血液或垂体催乳素水平的差异。下丘脑多巴胺活性被评估为催乳素水平变化的潜在机制。下丘脑酪氨酸羟化酶mRNA在两种遗传模型与野生型小鼠和下丘脑多巴胺和3,4-二羟基苯乙酸(DOPAC)含量测定雄性AgRP KO和野生型小鼠,但都没有显着差异。然而,这些结果并不排除多巴胺活性的变化,因为没有直接研究多巴胺代谢率。这是第一项研究表明,基线和应激诱导的催乳素释放和垂体催乳素含量减少与黑皮质素系统的遗传改变的小鼠,并表明下丘脑黑皮质素活性的变化可能反映在血清催乳素水平的测量。
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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期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
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