Effect of ovarian aging on androgen biosynthesis in a cynomolgus macaque model.
Effect of ovarian aging on androgen biosynthesis in a cynomolgus macaque model.
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DOI：
10.3109/13697137.2011.571321
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发表时间：
2012-02
期刊：
影响因子：
--
通讯作者：
Appt SE
中科院分区：
文献类型：
--
作者：
Ethun KF;Wood CE;Parker CR Jr;Kaplan JR;Chen H;Appt SE
雄激素在慢性疾病发病机制、认知功能和更年期性欲中的作用越来越受到关注。本研究的目的是描述猕猴卵巢中雄激素蛋白的分布和表达，并探讨血清雄激素浓度，卵泡数量和雄激素生成在衰老猕猴卵巢中的持久性之间的关系。受试者为26只成年雌性食蟹猴。对卵巢进行细胞色素P450 17α-羟化酶/17-20裂解酶（P450 c17）、3β-羟基类固醇脱氢酶（3βHSD）和细胞色素b5（cytb 5）免疫染色。根据原始卵泡计数，将动物分为三分位数（低（≤200）、中等（226-1232）和高（2372-4356）），以评价卵巢切除术后雄激素染色的差异和血清雄激素浓度的变化。P450 c17和cytb 5在生长卵泡内膜层中的阳性免疫染色持续存在于晚期闭锁卵泡和次级间质细胞（残留基质细胞）中。卵泡数量少的卵巢与生长卵泡数量较多的卵巢相比，所有雄激素蛋白的染色较少。cytb 5的免疫染色是最可靠的卵巢中持续雄激素发生的标记，原始卵泡数量最少（<100），基质细胞残留。在卵巢切除术后，在原始卵泡数量低、中、高的猴子中分别观察到睾酮（− 27.7%、− 30.8%、−27.5%; p < 0.01）和雄烯二酮（− 33.4%、− 35.7%、−46.0%; p < 0.01）显著降低。尽管卵泡数量较少，但老化的猕猴卵巢保留了残留基质细胞内雄激素生成所需的蛋白质，并有助于外周雄激素浓度。
The role of androgens in chronic disease pathogenesis, cognitive function and libido during menopause is of increasing interest. The aim of this study was to characterize the distribution and expression of androgenic proteins in the macaque ovary and to investigate the relationship between serum androgen concentrations, follicle number, and the persistence of androgenesis in the aging macaque ovary. The subjects were 26 adult female cynomolgus macaques. Ovaries were immunostained for cytochrome P450 17α-hydroxylase/17–20 lyase (P450c17), 3β-hydroxysteroid dehydrogenase (3βHSD), and cytochrome b5 (cytb5). Based on primordial follicle counts, animals were divided into tertiles (low (≤200), intermediate (226–1232), and high (2372–4356)) to evaluate differences in androgen staining and changes in serum androgen concentrations following ovariectomy. Positive immunostaining for P450c17 and cytb5 within the theca interna layer of growing follicles persisted in advanced atretic follicles and secondary interstitial cells (residual stromal cells). Ovaries with low follicle numbers had less staining for all androgenic proteins compared to ovaries with higher numbers of growing follicles. Immunostaining for cytb5 was the most reliable marker for persistent androgenesis in ovaries with minimal primordial follicle numbers (<100) and residual stromal cells. Following ovariectomy, a significant decrease in testosterone (−27.7%, −30.8%, −27.5%; p < 0.01) and androstenedione (−33.4%, −35.7%, −46.0%; p < 0.01) was observed in monkeys with low, intermediate, and high primordial follicle counts, respectively. Despite low follicle numbers, the aging macaque ovary retains the necessary proteins for androgenesis within residual stromal cells and contributes to peripheral androgen concentrations.
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