PREPUBERTAL OVARIAN-FUNCTION IS FINELY REGULATED BY DIRECT ADRENERGIC INFLUENCES - ROLE OF NORADRENERGIC INNERVATION
PREPUBERTAL OVARIAN-FUNCTION IS FINELY REGULATED BY DIRECT ADRENERGIC INFLUENCES - ROLE OF NORADRENERGIC INNERVATION
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DOI：
10.1210/endo-114-5-1845
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发表时间：
1984-01-01
期刊：
影响因子：
4.8
通讯作者：
OJEDA, SR
中科院分区：
文献类型：
--
作者：
AGUADO, LI;OJEDA, SR
在大鼠中，支配非血管卵巢组织的肾上腺素能纤维的主要来源是卵巢上级神经（SON）。为了确定SON对青春期前卵巢功能的影响，因此，对青春期的时间，进行了几个实验。在幼年早期大鼠（第24天）的SON横断导致卵巢去甲肾上腺素（NE）含量超过60%的消耗，但既不影响阴道开放的时间，也不影响第一次排卵。然而，SON部分产生β-IFN-γ 2 - 2的2倍增加。肾上腺素能受体密度，亲和力没有变化，表明去神经支配的超敏反应已经发展。通过体外培养分离的细胞从卵巢颗粒细胞中去除所有肾上腺素能影响，产生β-肾上腺素能的显著增加。肾上腺素能受体数目在72 h达到高峰。尽管受体含量升高，β-肾上腺素能激动剂锌特罗不诱导孕酮释放，除非细胞预先暴露于生理浓度的FSH 48小时。NE和肾上腺素都以剂量相关的方式下调受体，而不影响受体亲和力。为了检验卵巢去神经导致类固醇对肾上腺素能刺激更敏感的假设，构建了一个模型，其中细胞同时暴露于FSH和NE或肾上腺素（神经支配细胞）或仅暴露于FSH（去神经细胞）48小时。随后通过将细胞与锌特罗孵育24小时来测量对肾上腺素能刺激的反应。锌特罗是非常有效的引发孕酮释放从失神经细胞，但未能做到这一点，在神经支配的细胞。此外，激动剂增加了前者细胞中的cAMP，但在后者中无效，表明先前暴露于儿茶酚胺使与β-腺苷酸环化酶偶联的腺苷酸环化酶脱敏。肾上腺素能受体位点。显然，在青春期前成熟期间，通过SON到达卵巢的去甲肾上腺素能纤维可以通过调节功能性β-肾上腺素受体的数量来改变卵巢对儿茶酚胺的类固醇生成敏感性。肾上腺素能受体SON去神经支配明显未能改变卵巢类固醇生成的成熟和青春期的时间可能是由于去神经支配后代偿性超敏反应的发展。
In the rat, the main source of adrenergic fibers innervating nonvascular ovarian tissue is the superior ovarian nerve (SON). To determine the influence of the SON on prepubertal ovarian function and, hence, on the time of puberty, several experiments were conducted. Transection of the SON in early juvenile rats (day 24) led to more than 60% depletion in ovarian norepinephrine (NE) content, but affected neither the timing of vaginal opening nor that of 1st ovulation. SON section, however, produced a 2-fold increase in .beta.-adrenergic receptor density, with no change in affinity, suggesting that hypersensitivity by denervation had developed. Removal of all adrenergic influences from ovarian granulosa cells by culturing the isolated cells in vitro produced a striking increase in .beta.-adrenergic receptor number, which was maximal at 72 h. In spite of this elevated receptor content, the .beta.-adrenergic agonist Zinterol did not induce progesterone release unless the cells were previously exposed for 48 h to a physiological concentration of FSH. Both NE and epinephrine down-regulated the receptors in a dose-related manner, without affecting receptor affinity. To test the hypothesis that denervation of the ovary results in greater steroidal sensitivity to adrenergic stimulation, a model was constructed in which cells were simultaneously exposed to FSH and NE or epinephrine (innervated cells) or exposed only to FSH (denervated cells) for 48 h. The resposne to adrenergic stimulation was subsequently measured by incubating the cells with Zinterol for 24 h. Zinterol was highly effective in eliciting progesterone release from the denervated cells, but failed to do so in innervated cells. Additionally, the agonist increased cAMP in the former cells, but it was ineffective in the latter, indicating that prior exposure to catecholamines desensitized the adenylate cyclase enzyme coupled to .beta.-adrenergic receptor sites. Apparently, during prepubertal maturation, noradrenergic fibers reaching the ovary via the SON may modify ovarian steroidogenic sensitivity to catecholamines, by regulating the number of functional .beta.-adrenergic recetpros in the gland. The apparent failure of SON denervation to alter the maturation of ovarian steroidogenesis and the time of puberty may be due to development of compensatory hypersensitivity after the denervation.