The Ritchie Centre, Monash Institute of Medical Research, 27-31 Wright Street, Clayton, Melbourne, Victoria, Australia 3168.
Endocrinology. 2013 Mar;154(3):1190-201. doi: 10.1210/en.2012-1953. Epub 2013 Jan 25.
Synthesis of the androgen dehydroepiandrosterone (DHEA) by the fetal adrenal gland is important for placental estrogen production and may also be important for modulating the effects of glucocorticoids on the developing brain. The presence of cortisol in spiny mouse (Acomys cahirinus) blood led us to determine whether the adrenal gland of this precocial rodent also synthesized DHEA. Cytochrome P450 enzyme 17α-hydroxylase/17,20-lyase (P450c17), cytochrome-b5 (Cytb5), and 3β-hydroxysteroid dehydrogenase (3βHSD) were detected in the adrenal gland from 30 days gestation (term = 39 days), and DHEA, cortisol, and aldosterone were detected in fetal plasma from this time. Plasma DHEA concentrations increased 4-fold, whereas cortisol concentrations decreased from day 30 of gestation until the day of birth. Explant culture of fetal adrenal tissue showed that DHEA was produced from exogenous pregnenolone, and thus, the DHEA in the fetal circulation is likely to be of fetal origin. Clear zonation of the fetal adrenal cortex was evident by 38 days gestation when expression of Cytb5 was present throughout the cortex, and coexpression of P450c17 and Cytb5 occurred in the zona reticularis and fasciculata. 3βHSD was expressed in the cortex from at least 30 days gestation and decreased as term approached, consistent with the fall of cortisol in late gestation in this species. These results show that the spiny mouse adrenal gland, like that of the human fetus, can synthesize and secrete DHEA from at least 30 days (relative gestation length, 30 days of a 39-day gestation, 0.76) of gestation, and DHEA may have important roles in placental biosynthesis of estrogens and in modulating the actions of glucocorticoids in the developing brain in this species.
胎儿肾上腺合成雄激素脱氢表雄酮（DHEA）对于胎盘雌激素的产生很重要，并且可能对于调节糖皮质激素对发育中大脑的作用也很重要。在多刺鼠（Acomys cahirinus）的血液中存在皮质醇，这促使我们确定这种早产啮齿动物的肾上腺是否也合成了 DHEA。在妊娠 30 天（足月= 39 天）的肾上腺中检测到细胞色素 P450 酶 17α-羟化酶/17,20-裂解酶（P450c17）、细胞色素-b5（Cytb5）和 3β-羟甾脱氢酶（3βHSD），并且从此时开始在胎儿血浆中检测到 DHEA、皮质醇和醛固酮。血浆 DHEA 浓度增加了 4 倍，而皮质醇浓度从妊娠第 30 天到出生日下降。胎儿肾上腺组织的离体培养表明，DHEA 是由外源性孕烯醇酮产生的，因此，胎儿循环中的 DHEA 可能来自胎儿本身。到妊娠 38 天，胎儿肾上腺皮质的清晰分区已经很明显，此时 Cytb5 存在于整个皮质中，并且 P450c17 和 Cytb5 共同表达于网状带和束状带。从妊娠至少 30 天开始，3βHSD 在皮质中表达，并在接近足月时减少，与该物种妊娠晚期皮质醇下降的情况一致。这些结果表明，多刺鼠的肾上腺与人类胎儿的肾上腺一样，至少从妊娠 30 天（相对妊娠长度，妊娠 39 天的 30 天，0.76）开始就可以合成和分泌 DHEA，并且 DHEA 可能在胎盘雌激素的生物合成中以及在调节该物种发育中大脑中糖皮质激素的作用方面发挥重要作用。
