Belgorosky Alicia, Baquedano María Sonia, Guercio Gabriela, Rivarola Marco A
Endocrinology Department, Garrahan Pediatric Hospital, Buenos Aires, Argentina.
Rev Endocr Metab Disord. 2009 Mar;10(1):51-61. doi: 10.1007/s11154-008-9105-1.
Adrenarche is a process of postnatal sexual maturation occurring in higher primates, in which there is an increase in the secretion of adrenal androgens. It is the consequence of a process of postnatal organogenesis characterized by the development of a new zone in the adrenal cortex, the zona reticularis (ZR). The mechanism of this phenomenon remains poorly understood, suggesting that it might be a multifactorial event. A relationship between circulating IGF-I, insulin sensitivity, and adrenal androgens has been postulated. Boys and girls have different patterns of changes in insulin sensitivity at puberty, perhaps secondary to differences in the estrogen milieu. Estrogen effects may also play a role in premature adrenarche. Peripheral or local IGF-1 actions could regulate adrenal progenitor cell proliferation and migration. Since adrenal progenitor cells as well as IGF-I and the IGF-R1 are located in the outer zone of the adrenal cortex during childhood and adolescence, this peripheral cell layer, below the capsule, may contain undifferentiated progenitor cells. Therefore, the IGF-R1 signaling pathway might positively modulate the proliferation and migration of adrenal progenitor cell to stimulate the development of adrenal zones, including ZR. However, no evidence of a direct action of IGF-I on ZR was found. In addition, a role for estrogens in the ontogenesis of ZR is suggested by the presence of aromatase (CYP19) in the subcapsular zona glomerulosa and in the adrenal medulla. Estrogens produced locally could act on ZR by interacting with estrogen receptor beta (ERbeta), but not alpha, and membrane estrogen receptor GPR-30. An estradiol-induced increase in DHEA/cortisol ratio was indeed seen in cultures of adrenocortical cells from post-adrenarche adrenals. In summary, several lines of evidence point to the action of multiple factors, such as local adrenal maturational changes and peripheral metabolic signals, on postnatal human adrenal gland ZR formation.
肾上腺初现是高等灵长类动物出生后发生的性成熟过程，在此过程中肾上腺雄激素分泌增加。它是出生后器官发生过程的结果，其特征是肾上腺皮质出现一个新区域，即网状带（ZR）。这种现象的机制仍知之甚少，提示其可能是一个多因素事件。已推测循环中的胰岛素样生长因子-I（IGF-I）、胰岛素敏感性与肾上腺雄激素之间存在关联。男孩和女孩在青春期胰岛素敏感性的变化模式不同，这可能继发于雌激素环境的差异。雌激素效应也可能在性早熟中起作用。外周或局部的IGF-1作用可能调节肾上腺祖细胞的增殖和迁移。由于在儿童期和青春期肾上腺祖细胞以及IGF-I和IGF-R1位于肾上腺皮质的外层，因此在被膜下方的这个外周细胞层可能含有未分化的祖细胞。因此，IGF-R1信号通路可能正向调节肾上腺祖细胞的增殖和迁移，以刺激包括ZR在内的肾上腺区域的发育。然而，未发现IGF-I对ZR有直接作用的证据。此外，在被膜下的球状带和肾上腺髓质中存在芳香化酶（CYP19），提示雌激素在ZR的发生过程中起作用。局部产生的雌激素可能通过与雌激素受体β（ERβ）而非α以及膜雌激素受体GPR-30相互作用而作用于ZR。在肾上腺初现后的肾上腺皮质细胞培养物中确实观察到雌二醇诱导的脱氢表雄酮/皮质醇比值增加。总之，多条证据表明多种因素，如局部肾上腺成熟变化和外周代谢信号，对出生后人类肾上腺ZR的形成有作用。
