Hart John E
Endocrine Pharmaceuticals Limited, Wilderness End, Tadley Common Road, Tadley, Hampshire RG26 3TA, UK.
Med Hypotheses. 2014 Dec;83(6):775-86. doi: 10.1016/j.mehy.2014.10.009. Epub 2014 Oct 19.
There is evidence for an unrecognised classical hormone secreted by the mammalian gonad. This postulated hormone--'micrin' (pronounced 'my-crin')--represents the body's brake against tissue overgrowth. When oestrogens are administered in high doses to female rats there is a considerable (non-artefactual) increase in the relative size and weight of organs such as the pituitary, adrenals, uterus and liver--suggesting an organotrophic (organ-building) role for endogenous oestrogens. This effect is exaggerated if the animals are first ovariectomized, indicating the removal of a negative ovarian factor, micrin. These organ enlargements can be reduced by pretreating the rats with large doses of antioestrogens such as clomiphene and tamoxifen. This antiestrogenic blockade of exogenous oestrogens is itself blunted by prior removal of the ovaries. It is proposed that antioestrogens (e.g. tamoxifen in breast cancer treatment) antagonize the organotrophic effects of oestrogens by competing for the oestrogen receptor peripherally and centrally and via an increase in the secretion of ovarian micrin. It is deduced that micrin is the testicular 'inhibin' proposed in the 1930s, not the molecule that now bears that name, which acts at the pituitary tier as a downregulator of follicle-stimulating hormone. The hallmark of micrin deficiency in the male rat is a pituitary hypertrophy that follows castration. This is reversible with a steroid-depleted aqueous bovine testicular extract, the micrin within which suppresses the hypothalamus, normalizing the pituitary. Micrin probably acts as a brake on peripheral tissues directly but also indirectly at the meta-level via the hypothalamic-pituitary axis, resetting a hypothalamic 'organostat' controlling organ and tissue masses, part of the 'organotrophic system' of internal size regulation. Besides endocrine (circulating) micrin from the gonads there is probably paracrine (locally acting) micrin produced in the brain. This is involved in a somatic cueing system for puberty: the brake comes off at an appropriate body tissue mass disinhibiting the hypothalamus and accelerating the organism towards sexual maturity and full adult stature. This suggests the use in reproductive disorders of micrin-related drugs. These could also be inhibitors of breast, prostate and other cancers, while protecting the bone marrow via a trophic effect on the adrenals (the lack of which protection causes lethal bone marrow depression in oestrogen-treated ferrets and dogs). Benign prostatic hyperplasia is asserted to be a micrin deficiency disorder, involving insufficiently opposed androgen. The rise in cancers with age could be associated with a reduction in micrin protection and a relative lack of this hormone could partly explain why men die younger than women. Micrin is dissimilar in activity to any known molecule and could usefully be isolated, characterised and exploited therapeutically.
有证据表明哺乳动物性腺分泌一种未被识别的经典激素。这种假定的激素——“微泌素”（发音为“my - crin”）——代表了身体对组织过度生长的抑制作用。当给雌性大鼠高剂量注射雌激素时，垂体、肾上腺、子宫和肝脏等器官的相对大小和重量会有显著（非人为造成的）增加——这表明内源性雌激素具有促器官生长（器官构建）的作用。如果先对动物进行卵巢切除，这种效应会被放大，这表明卵巢中存在一种负面因子微泌素被去除了。通过用大剂量抗雌激素药物如克罗米芬和他莫昔芬预处理大鼠，可以减少这些器官的增大。卵巢切除预先进行会使这种对外源性雌激素的抗雌激素阻断作用本身减弱。有人提出抗雌激素药物（如乳腺癌治疗中的他莫昔芬）通过在周围和中枢与雌激素受体竞争，并通过增加卵巢微泌素的分泌来拮抗雌激素的促器官生长作用。据推断，微泌素就是20世纪30年代提出的睾丸“抑制素”，而不是现在被称为抑制素的那种作用于垂体水平作为促卵泡激素下调因子的分子。雄性大鼠微泌素缺乏的标志是阉割后垂体肥大。用不含类固醇的牛睾丸水提取物可使其恢复正常，其中的微泌素可抑制下丘脑，使垂体恢复正常。微泌素可能直接对周围组织起抑制作用，也可能通过下丘脑 - 垂体轴在更高层面间接起作用，重置控制器官和组织质量的下丘脑“器官调节器”，这是内部大小调节“促器官生长系统”的一部分。除了性腺分泌的内分泌（循环）微泌素外，大脑中可能还产生旁分泌（局部作用）微泌素。这参与了青春期的一种体细胞信号系统：当身体组织质量达到适当水平时，抑制作用解除，从而解除对下丘脑的抑制，促使机体向性成熟和完全成年身高发展。这提示了微泌素相关药物在生殖系统疾病中的应用。这些药物也可能是乳腺癌、前列腺癌和其他癌症的抑制剂，同时通过对肾上腺的营养作用来保护骨髓（雌激素处理的雪貂和狗缺乏这种保护会导致致命的骨髓抑制）。良性前列腺增生被认为是一种微泌素缺乏症，涉及雄激素拮抗不足。癌症随年龄增长的增加可能与微泌素保护作用的降低有关，这种激素的相对缺乏可能部分解释了为什么男性比女性寿命短。微泌素的活性与任何已知分子都不同，有望被分离、鉴定并用于治疗。
