Another role highlighted for estrogens in the male: sexual behavior.
Another role highlighted for estrogens in the male: sexual behavior.
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雌激素对男性的另一个突出作用是：性行为。
DOI：
10.1073/pnas.011526097
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发表时间：
2000
影响因子：
11.1
通讯作者：
Davis,SR
中科院分区：
文献类型：
--
作者：
Simpson,ER;Davis,SR
缺乏雌激素代表的模型，无论是合成失败还是反应不敏感，都为雌激素在男性和女性中的作用提供了新的，在某些方面违反直觉的见解。在自然突变中，目前有1名男性被鉴定为雌激素受体突变，多达10名个体编码芳香化酶基因突变，芳香化酶是负责雌激素生物合成的酶。其中2人是男性。此外，有多种小鼠模型涉及靶向基因破坏。除了芳香酶基因敲除（ArKO; ref. 2）外，这些基因还包括ER æ （ERKO; ref. 1）和ERß （ERKO; ref. 2）基因的敲除，以及ER æ和ERß （ßERKO; ref. 3）基因的双敲除。4 - 6)老鼠。对这些突变导致的表型分析揭示了男性和女性不同程度和类型的不育，这取决于所涉及的突变。脂质和碳水化合物表型涉及胰岛素抵抗、高脂血症和高瘦素血症的肥胖增加，以及社会和性行为模式的紊乱（6-8）。这些研究表明，雌激素在生理上的作用比以前认为的更广泛，而且这些雌激素通常是非两性二态的。事实上，雌激素和雄激素的传统概念现在受到挑战，因为雌二醇在调节精子发生中的作用（3,9）更适合归类为雄激素。近年来出现的另一个重要概念是，在绝经后的女性和男性中，雌激素主要是作为旁分泌甚至是分泌因子发挥作用（10,11）。因此，绝经后，当卵巢停止产生雌二醇，循环中的雌激素水平极低时，雌激素在卵巢外的各种部位产生，局部刺激邻近细胞，甚至刺激产生雌激素的细胞。这些部位包括骨
Models of lack of estrogen represen-tation, whether they be failure of synthesis or insensitivity of response, have provided new, and in some respects counterintuitive, insights into the roles of estrogens in both males and females. Among the natural mutations, there is currently 1 man identified with a mutation of the estrogen receptor ɑ (ERɑ) and up to 10 individuals with mutations of the gene encoding aromatase, the enzyme responsible for estrogen biosynthesis. Of these, 2 are men. In addition, there are various mouse models involving targeted gene disruption. These include knock-outs of the ERɑ (ɑERKO; ref. 1) and ERß (ßERKO; ref. 2) genes as well as the double ERɑ and ERß (ɑßERKO; ref. 3) knockout, in addition to the aromatase knockout (ArKO; refs. 4–6) mice. Analysis of the phenotypes resulting from these mutations has revealed various degrees and types of infertility in both male and female, depending on the mutation involved. Lipid and carbohydrate phenotypes involving increased adiposity with insulin resistance, hyperlipidemia and hyperleptinemia as well as disturbances in behavior patterns, both social and sexual, have also been described (6–8). These studies reveal that estrogens have more extensive roles in physiology than was previously thought, and moreover these are frequently of a non-sexually dimorphic nature. Indeed the traditional concepts of the terms estrogen and androgen are now challenged because the role of estradiol in the regulation of spermatogenesis (3, 9) is one that would more properly be classified as androgenic.Another important concept that has emerged in recent years is that in postmenopausal women, as well as in men, estrogens function primarily as paracrine or even intracrine factors (10, 11). Thus, following menopause, when the ovaries cease to produce estradiol and circulating estrogen levels are extremely low, estrogen is produced in a variety of extragonadal sites and acts locally to stimulate adjacent cells or even the cells in which it is produced. These sites include osteo-