Carmignac D F, Bennett P A, Robinson I C
Division of Neurophysiology, National Institute for Medical Research, London, United Kingdom.
Endocrinology. 1998 Aug;139(8):3590-6. doi: 10.1210/endo.139.8.6148.
In addition to stimulating GH release, GH secretagogues such as GH-releasing peptide-6 (GHRP-6) stimulate small amounts of ACTH and PRL release. Although the effects on ACTH have recently been studied, there is little information about the effects of GHRP-6 on PRL. We have now studied GHRP-6-induced GH and PRL release and their regulation by estrogen (E2) in anesthetized male and female rats and in GH-deficient dwarf (dw/dw) rats that maintain high pituitary PRL stores and show elevated hypothalamic GH secretagogue receptor expression. Whereas GHRP-6 (0.1-2.5 microg, i.v.) did not induce PRL release in normal male or female rats, significant PRL responses were observed in dw/dw females. These responses were abolished by ovariectomy and could be strongly induced in male dw/dw rats by E2 treatment. These effects could be dissociated from GHRP-6-induced GH release in the same animals, but not from PRL release induced by TRH, which was also abolished by ovariectomy and induced in males by E2 treatment. However, the effects of GHRP-6 on PRL were unlikely to be mediated by TRH because in the same animals, TSH levels were unaffected by GHRP-6 whereas they were increased by TRH. The increased PRL response could reflect an increase in GH secretagogue receptor expression that was observed in the arcuate and ventromedial nuclei of E2-treated rats. Our results suggest that the minimal PRL-releasing activity of GHRP-6 in normal rats becomes prominent in GH-deficient female dw/dw rats and is probably exerted directly at the pituitary; these GHRP-6 actions may be modulated by E2 at both hypothalamic and pituitary sites.
除了刺激生长激素（GH）释放外，生长激素促分泌素如生长激素释放肽-6（GHRP-6）还能刺激少量促肾上腺皮质激素（ACTH）和催乳素（PRL）释放。尽管最近对其对ACTH的作用进行了研究，但关于GHRP-6对PRL的作用却知之甚少。我们现在研究了在麻醉的雄性和雌性大鼠以及生长激素缺乏的侏儒（dw/dw）大鼠中，GHRP-6诱导的GH和PRL释放及其受雌激素（E2）的调节情况。这些dw/dw大鼠垂体中PRL储备较高，下丘脑生长激素促分泌素受体表达升高。在正常雄性或雌性大鼠中，GHRP-6（0.1 - 2.5微克，静脉注射）不会诱导PRL释放，但在dw/dw雌性大鼠中观察到了显著的PRL反应。这些反应在卵巢切除后消失，而通过E2处理可在雄性dw/dw大鼠中强烈诱导出这些反应。在同一动物中，这些作用可与GHRP-6诱导的GH释放相分离，但不能与促甲状腺激素释放激素（TRH）诱导的PRL释放相分离，TRH诱导的PRL释放也在卵巢切除后消失，并在雄性大鼠中通过E2处理诱导产生。然而，GHRP-6对PRL的作用不太可能由TRH介导，因为在同一动物中，促甲状腺激素（TSH）水平不受GHRP-6影响，而受TRH升高。PRL反应增加可能反映了在E2处理大鼠的弓状核和腹内侧核中观察到的生长激素促分泌素受体表达增加。我们的结果表明，GHRP-6在正常大鼠中最小的PRL释放活性在生长激素缺乏的雌性dw/dw大鼠中变得显著，并且可能直接作用于垂体；这些GHRP-6的作用可能在下丘脑和垂体部位都受到E2的调节。
