Faculty of Medicine and Health, University of New South Wales,Sydney, New South Wales, Australia.
Department of Diabetes and Endocrinology, Blacktown Hospital, Blacktown, New South Wales, Australia.
Eur J Endocrinol. 2021 May 6;184(6):R269-R278. doi: 10.1530/EJE-21-0155.
There is a strong biological link between the growth hormone (GH) and gonadal systems in growth, development and metabolism; however, regulatory interactions are poorly understood. Advances in estrogen biology and endocrine physiology have provided insights into mechanistic links between the two systems. Estrogens are synthesized from androgens by aromatase which is widely distributed in extragonadal tissues. Local generation of estrogens raise the possibility of paracrine control as an additional level to classical endocrine regulation of the GH system. To explore the mechanistic links, we review the pharmacology of estrogen, the effects of estrogen replacement, antagonism, and the impact of aromatase inhibition on the GH system as well as the metabolic sequelae. In men, estrogens derived from androgens drive the central secretion of GH, independent of the androgen receptor. In hypogonadal women, physiological replacement via a parenteral route evokes no effect while estrogen receptor antagonism and estrogen deprivation induce disparate effects, providing no consistent evidence that estrogens regulate the central secretion of GH via paracrine or endocrine mechanisms. However, delivery of estrogen by the oral route inhibits hepatic IGF-1 production, in turn increasing GH secretion via reduced feedback inhibition. This endocrine route-dependent effect of oral estrogen compounds on hepatic function induces detrimental metabolic effects on hypogonadal women. In conclusion, estrogens regulate the secretion and action of GH via complex paracrine and endocrine interactions and impart metabolic effects in a route- and gender-dependent manner. The metabolic sequelae of compounds mimicking, antagonizing, or depleting estrogens, should be considered in tailoring and optimizing their use.
在生长、发育和代谢过程中，生长激素（GH）和性腺系统之间存在着强烈的生物学联系；然而，调控相互作用仍知之甚少。雌激素生物学和内分泌生理学的进展为这两个系统之间的机制联系提供了深入了解。雌激素是由广泛分布于性腺外组织的芳香化酶从雄激素合成的。局部产生的雌激素增加了旁分泌控制作为GH 系统经典内分泌调节的附加水平的可能性。为了探讨机制联系，我们回顾了雌激素的药理学、雌激素替代、拮抗作用以及芳香化酶抑制对 GH 系统的影响以及代谢后果。在男性中，雄激素衍生的雌激素驱动 GH 的中枢分泌，而与雄激素受体无关。在性腺功能减退的女性中，通过肠外途径进行生理替代没有效果，而雌激素受体拮抗和雌激素剥夺则引起不同的效果，没有一致的证据表明雌激素通过旁分泌或内分泌机制调节 GH 的中枢分泌。然而，通过口服途径给予雌激素会抑制肝脏 IGF-1 的产生，从而通过减少反馈抑制增加 GH 的分泌。这种口服雌激素化合物对肝脏功能的内分泌途径依赖性作用会对性腺功能减退的女性产生有害的代谢影响。总之，雌激素通过复杂的旁分泌和内分泌相互作用调节 GH 的分泌和作用，并以途径和性别依赖的方式产生代谢影响。模拟、拮抗或耗尽雌激素的化合物的代谢后果应在定制和优化其使用时加以考虑。
