Melvin J E, Hamill R W
Monroe Community Hospital, University of Rochester Medical Center, New York 14642.
J Neurosci. 1989 Feb;9(2):736-42. doi: 10.1523/JNEUROSCI.09-02-00736.1989.
Previous studies indicate that the major pelvic ganglion (PG) is dependent on testosterone for normal development. Tyrosine hydroxylase (T-OH), DOPA decarboxylase, and choline acetyltransferase (CAT) activities are significantly reduced by postnatal castration on day 10-11, while testosterone replacement therapy reversed all developmental enzyme activity deficits (Melvin and Hamill, 1987). In the present studies castration on the day of birth combined with various testosterone-replacement paradigms produced effects demonstrating that the PG is sensitive to testosterone dosage and time of administration during early postnatal development. Gonadal hormone replacement experiments show that the androgens testosterone and dihydrotestosterone were effective in restoring T-OH and CAT activity deficits produced by neonatal castration. Estrogen therapy reversed the deficits in CAT activity, but was ineffective in reversing the alterations in T-OH activity. Treatment of pregnant dams with the anti-androgen flutamide altered the ontogeny of T-OH and CAT activities in pups despite replacement therapy on the day of birth. Thus, androgen-critical periods exist prenatally as well as postnatally. These studies suggest that the organization of PG development is critically dependent on both the time of exposure and dose of testosterone. Prenatal and postnatal critical periods appear to exist. In addition, the lack of an effect of estradiol on tyrosine hydroxylase activity suggests that androgens are specifically responsible for organizing the noradrenergic development of the PG.
先前的研究表明,主盆腔神经节(PG)的正常发育依赖于睾酮。产后第10 - 11天去势会使酪氨酸羟化酶(T - OH)、多巴脱羧酶和胆碱乙酰转移酶(CAT)的活性显著降低,而睾酮替代疗法可逆转所有发育性酶活性缺陷(梅尔文和哈米尔,1987年)。在本研究中,出生当天去势并结合各种睾酮替代模式所产生的效应表明,PG在出生后早期发育过程中对睾酮剂量和给药时间敏感。性腺激素替代实验表明,雄激素睾酮和双氢睾酮可有效恢复新生期去势所致的T - OH和CAT活性缺陷。雌激素疗法可逆转CAT活性缺陷,但对逆转T - OH活性改变无效。尽管在出生当天进行了替代疗法,但用抗雄激素氟他胺处理怀孕母鼠会改变幼崽T - OH和CAT活性的个体发生。因此,雄激素关键期在产前和产后均存在。这些研究表明,PG发育的组织过程严重依赖于睾酮的暴露时间和剂量。产前和产后关键期似乎都存在。此外,雌二醇对酪氨酸羟化酶活性缺乏影响表明,雄激素是PG去甲肾上腺素能发育组织的特异性原因。