Caminos J E, Nogueiras R, Blanco M, Seoane L M, Bravo S, Alvarez C V, García-Caballero T, Casanueva F F, Diéguez C
Department of Physiology, University of Santiago de Compostela, School of Medicine, 15705 Santiago de Compostela, Spain.
Endocrinology. 2003 Nov;144(11):5089-97. doi: 10.1210/en.2003-0529. Epub 2003 Aug 7.
Ghrelin, a 28-amino-acid acylated peptide, strongly stimulates GH release and food intake. In the present study, we found that ghrelin is expressed in somatotrophs, lactotrophs, and thyrotrophs but not in corticotrophs or gonadotrophs of rat pituitary. Persistent expression of the ghrelin gene is found during postnatal development in male and female rats, although the levels significantly decrease in both cases from pituitaries of 20-d-old rats onward, but at 60 d old, the levels were higher in male than female rats. This sexually dimorphic pattern appears to be mediated by estrogens because ovariectomy, but not orchidectomy, increases pituitary ghrelin mRNA levels. Taking into account that somatotroph cell function is markedly influenced by thyroid hormones, glucocorticoids, GH, and metabolic status, we also assessed such influence. We found that ghrelin mRNA levels decrease in hypothyroid- and glucocorticoid-treated rats, increase in GH-deficient rats (dwarf rats), and remain unaffected by food deprivation. In conclusion, we have defined the specific cell types that express ghrelin in the rat anterior pituitary gland. These data provide direct morphological evidence that ghrelin may well be acting in a paracrine-like fashion in the regulation of anterior pituitary cell function. In addition, we clearly demonstrate that pituitary ghrelin mRNA levels are age and gender dependent. Finally, we show that pituitary ghrelin mRNA levels are influenced by alteration on thyroid hormone, glucocorticoids, and GH levels but not by fasting, which indicates that the regulation of ghrelin gene expression is tissue specific.
胃饥饿素是一种由28个氨基酸组成的酰化肽，能强烈刺激生长激素释放和食物摄入。在本研究中，我们发现胃饥饿素在大鼠垂体的生长激素细胞、催乳素细胞和促甲状腺激素细胞中表达，但在促肾上腺皮质激素细胞或促性腺激素细胞中不表达。在雄性和雌性大鼠出生后的发育过程中，胃饥饿素基因持续表达，尽管从20日龄大鼠的垂体开始，两种情况下其水平均显著下降，但在60日龄时，雄性大鼠的水平高于雌性大鼠。这种性别差异模式似乎是由雌激素介导的，因为卵巢切除可增加垂体胃饥饿素mRNA水平，而睾丸切除则无此作用。鉴于生长激素细胞的功能受到甲状腺激素、糖皮质激素、生长激素和代谢状态的显著影响，我们也评估了这些因素的影响。我们发现，甲状腺功能减退和糖皮质激素处理的大鼠中胃饥饿素mRNA水平降低，生长激素缺乏的大鼠（侏儒大鼠）中胃饥饿素mRNA水平升高，而禁食对其无影响。总之，我们确定了大鼠垂体前叶中表达胃饥饿素的特定细胞类型。这些数据提供了直接的形态学证据，表明胃饥饿素很可能以旁分泌样方式调节垂体前叶细胞功能。此外，我们清楚地证明垂体胃饥饿素mRNA水平与年龄和性别有关。最后，我们表明垂体胃饥饿素mRNA水平受甲状腺激素、糖皮质激素和生长激素水平变化的影响，但不受禁食影响，这表明胃饥饿素基因表达的调节具有组织特异性。
