Mayerhofer A, Smith G D, Danilchik M, Levine J E, Wolf D P, Dissen G A, Ojeda S R
Division of Neuroscience, Oregon Regional Primate Research Center, Beaverton, OR 97006, USA.
Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10990-5. doi: 10.1073/pnas.95.18.10990.
Catecholamines, thought to derive from the extrinsic innervation of the ovary, participate in the regulation of ovarian development and mature gonadal function. Recently, intraovarian neurons containing tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, were described in the ovary of nonhuman primates. We now show that the primate ovary expresses both the genes encoding TH and dopamine beta-hydroxylase (DBH), the key enzymes in norepinephrine (NE) biosynthesis. Ovarian neurons were identified as a site of TH and DBH gene expression, and surprisingly, oocytes were identified as an exclusive site of DBH synthesis. Oocytes contain neither TH mRNA nor protein, indicating that they are unable to synthesize dopamine (DA). They did, however, express a DA transporter gene identical to that found in human brain. The physiological relevance of this transporter system and DBH in oocytes was indicated by the ability of isolated oocytes to metabolize exogenous DA into NE. Isolated follicles containing oocytes-but not those from which the oocytes had been removed-responded to DA with an elevation in cAMP levels; this elevation was prevented by propranolol, a beta-adrenoreceptor antagonist. The results suggest that oocytes and somatic cells are linked by a neuroendocrine loop consisting of NE synthesized in oocytes from actively transported DA and cAMP produced by somatic follicular cells in response to NE-induced beta-adrenoreceptor activation.
儿茶酚胺被认为源自卵巢的外在神经支配，参与卵巢发育和成熟性腺功能的调节。最近，在非人灵长类动物的卵巢中发现了含有酪氨酸羟化酶（TH）的卵巢内神经元，酪氨酸羟化酶是儿茶酚胺生物合成中的限速酶。我们现在表明，灵长类动物卵巢表达编码TH和多巴胺β-羟化酶（DBH）的基因，DBH是去甲肾上腺素（NE）生物合成中的关键酶。卵巢神经元被确定为TH和DBH基因表达的位点，令人惊讶的是，卵母细胞被确定为DBH合成的唯一位点。卵母细胞既不含有TH mRNA也不含有TH蛋白，这表明它们无法合成多巴胺（DA）。然而，它们确实表达了一种与人脑相同的DA转运体基因。分离的卵母细胞能够将外源性DA代谢为NE，这表明了该转运体系统和DBH在卵母细胞中的生理相关性。含有卵母细胞的分离卵泡（而不是去除卵母细胞后的卵泡）对DA的反应是cAMP水平升高；这种升高被β-肾上腺素能受体拮抗剂普萘洛尔所阻止。结果表明，卵母细胞和体细胞通过一个神经内分泌环路相连，该环路由卵母细胞中从主动转运的DA合成的NE以及卵泡体细胞响应NE诱导的β-肾上腺素能受体激活而产生的cAMP组成。
