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Mechanism of action of gonadotropins. 促性腺激素的作用机制。
Pub Date : 1976-01-01
B B Saxena, P Rathnam
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引用次数: 0
Control of prolactin secretion by the hypothalamic catecholamines. 下丘脑儿茶酚胺控制催乳素分泌。
Pub Date : 1976-01-01
R M MacLeod, I Login

The neuroendocrine control of prolactin secretion is very complex. Even though the hypothalamus exerts a profound inhibitory influence upon the secretion of this hormone, the mechanism(s) involved is poorly understood. The cerebrospinal fluid seems to be becoming increasingly important as regards neuroendocrine regulatory mechanisms involving prolactin. Pharmacological agents such as apomorphine and many of the ergot alkaloids are very effective inhibitors of the secretion of prolactin. Still other pharmacological agents such as DMPEA, alpha-methyldopa, reserpine, and certain of the phenothiazines are very effective in causing a stimulation of prolactin secretion.

神经内分泌对催乳素分泌的控制是非常复杂的。尽管下丘脑对这种激素的分泌具有深远的抑制作用,但其机制尚不清楚。在涉及催乳素的神经内分泌调节机制方面,脑脊液似乎变得越来越重要。药物制剂,如阿波啡和许多麦角生物碱是非常有效的抑制剂分泌催乳素。还有其他药物如DMPEA, α -甲基多巴,利血平和某些吩噻嗪类药物在刺激催乳素分泌方面非常有效。
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引用次数: 0
Antiandrogens. 抗雄激素。
Pub Date : 1976-01-01
R O Neri

Many antiandrogens, mainly steroidal and some nonsteroidal agents, have been synthesized and tested in several available biological assays. Unfortunately, many of these compounds have other biological activities which make it difficult to ascertain the precise mechanism of antiandrogenic action. The blocking of androgen action can be accomplished by a number of ways: (1) the inhibition of gonadotropin release and/or synthesis, (2) the interference with testosterone and/or dihydrotestosterone biosynthesis, (3) the blocking of protein synthesis, and (4) the competition with androgens at receptor sites. Although the major reason for the development of antiandrogens is to utilize them in certain clinical situations, some have become important tools in studying androgen action, particularly on the molecular level. The clinical effectiveness of some antiandrogens in prostatic hyperplasias, hirsutism, and acne represents an important advance in therapeutics, but the search for more potent antiandrogens with minimal side effects should continue.

许多抗雄激素,主要是甾体和一些非甾体药物,已经合成并在几种可用的生物分析中进行了测试。不幸的是,许多这些化合物具有其他生物活性,这使得很难确定抗雄激素作用的确切机制。雄激素作用的阻断可以通过以下几种方式实现:(1)抑制促性腺激素的释放和/或合成,(2)干扰睾酮和/或双氢睾酮的生物合成,(3)阻断蛋白质合成,(4)在受体位点与雄激素竞争。虽然开发抗雄激素的主要原因是为了在某些临床情况下利用它们,但一些抗雄激素已成为研究雄激素作用的重要工具,特别是在分子水平上。一些抗雄激素治疗前列腺增生、多毛症和痤疮的临床疗效代表了治疗学的重要进展,但寻找副作用最小的更有效的抗雄激素应继续进行。
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引用次数: 0
Pineal factors in the control of testicular function. 松果体因子控制睾丸功能。
Pub Date : 1976-01-01
G A Kinson

The mammalian pineal gland has become firmly established as a neuroendocrine structure possessing the ability to influence the functions of the sex glands. There is substantial evidence in the literature that pineal factors also affect the activities of other endocrine systems. The pineal gland is thus conceivably far-reaching in its regulatory actions on physiological function, involving actions on the adrenal cortex, the thyroid, and parathyroid glands as well as the gonads of both sexes. The pineal gland of the hamster and the rat responds to environmental influences, particularly changes in length of the daily photoperiod, and in turn exerts regulatory effects on the activity of the testis. This relation is much more sensitive in the hamster where lack of adequate illumination stimulates pineal antigonadal activity to produce inhibition of both testicular gametogenesis and androgenesis. Involvement of the pineal in these responses to darkness or blinding has been clearly demonstrated by the negating effects of its removal. The physiological role of the pineal in regulating seasonal changes in testicular activity and reproductive capacity of the hamster has now been formulated (Reiter, 1973a, 1973b). The laboratory rat, a continuous breeder, is far less sensitive to lack of photic input. Surgical and environmental manipulations involving altered pineal activity invariably lead to less dramatic changes in various parameters of male reproductive function. The evidence would seem to indicate that pineal function in the rat is primarily related to the regulation of testicular endocrine function. Consequently, its physiological role may be associated with seasonal changes in libido in relation to environmental influences, by virtue of the action of pineal factors on androgen status. Spermatogenesis, on the other hand, was unaffected for periods as long as 1 year after the blinding of rats at the time of puberty (Kinson and Liu, 1974). There is evidence that the pineal gland has a part to play in the timing of puberty in the rat and in circadian variations in testosterone levels in the adult animal. Two groups of compounds have been identified as pineal agents and possibly pineal hormones. While the indoles have been more widely investigated as pineal antigonadal factors, the involvement of polypeptides in pineal actions was indicated a decade ago and these compounds are now receiving vigorous attention. Pineal factors influence testicular function by interaction with the neuroendocrine system to affect pituitary gonadotropin secretion. The higher neural centers appear to be responsive to indoles and via the releasing factors give rise to changes in pituitary content and circulating levels of FSH and LH. Prolactin also has been shown to respond to change in ambient lighting and to pinealectomy. Partially purified polypeptide fractions are now claimed to be considerably more potent antigonadotropically than melatonin, the indole most favored as

哺乳动物松果体作为一种具有影响性腺功能能力的神经内分泌结构已经得到了牢固的确立。文献中有大量证据表明松果体因子也影响其他内分泌系统的活动。因此,可以想象,松果体对生理功能的调节作用是深远的,包括对肾上腺皮质、甲状腺、甲状旁腺以及两性性腺的作用。仓鼠和大鼠的松果体对环境的影响作出反应,特别是每天光周期长度的变化,并反过来对睾丸的活动施加调节作用。这种关系在仓鼠中更为敏感,因为缺乏足够的光照会刺激松果体的抗性腺活性,从而抑制睾丸配子发生和雄激素发生。松果体参与这些对黑暗或致盲的反应已经被移除松果体的负面影响清楚地证明了。松果体在调节仓鼠睾丸活动和生殖能力的季节性变化中的生理作用现已被阐明(Reiter, 1973a, 1973b)。实验室的大鼠是连续繁殖的,对缺乏光输入的敏感程度要低得多。涉及改变松果体活动的手术和环境操作总是导致男性生殖功能的各种参数发生较小的变化。这些证据似乎表明,大鼠的松果体功能主要与睾丸内分泌功能的调节有关。因此,由于松果体因子对雄激素状态的作用,其生理作用可能与环境影响下性欲的季节性变化有关。另一方面,在大鼠青春期失明后长达1年的时间里,精子发生都没有受到影响(Kinson and Liu, 1974)。有证据表明,松果体在大鼠的青春期时间和成年动物睾酮水平的昼夜变化中起着一定的作用。两组化合物已被确定为松果体制剂和可能的松果体激素。虽然吲哚作为松果体抗性腺因子已被广泛研究,但多肽在松果体活动中的参与在十年前就被指出,这些化合物现在受到了大力关注。松果体因子通过与神经内分泌系统相互作用影响垂体促性腺激素分泌,从而影响睾丸功能。高级神经中枢似乎对吲哚有反应,并通过释放因子引起垂体含量和循环FSH和LH水平的变化。催乳素也被证明对环境光照的变化和松果体切除术有反应。部分纯化的多肽组分现在被声称比褪黑激素更有效的抗促性腺激素,作为松果体激素最受欢迎的吲哚…
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引用次数: 0
Androgens and estrogens in prostatic neoplasia. 前列腺肿瘤中的雄激素和雌激素。
Pub Date : 1976-01-01
M G Mawhinney, J A Belis
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引用次数: 0
Regulation of cyclic nucleotide and prostaglandin metabolism in sex steroid-dependent cells. 性类固醇依赖细胞中环核苷酸和前列腺素代谢的调节。
Pub Date : 1976-01-01
R L Singhal, B K Tsang, D J Sutherland
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引用次数: 0
Human gonadotropins: biochemical, immunological, and clinical aspects. 人促性腺激素:生化、免疫学和临床方面。
Pub Date : 1976-01-01
W R Butt

Methodologies for the extraction of both pituitary and urinary gonadotropins are described. The chemical composition of some of the gonadotropins is discussed, and the significance of the subunit structures is reviewed. Immunological properties of the gonadotropins are discussed from the standpoint of antisera and procedures involving radioimmunoassay. Finally, certain clinical conditions which are characterized by fluctuations in gonadotropin levels are discussed.

描述了提取垂体和尿促性腺激素的方法。讨论了一些促性腺激素的化学组成,并对亚基结构的意义进行了综述。从抗血清和放射免疫测定的角度讨论了促性腺激素的免疫学特性。最后,讨论了以促性腺激素水平波动为特征的某些临床条件。
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引用次数: 0
Control of proliferative growth in androgen responsive organs and neoplasms. 雄激素反应性器官和肿瘤的增殖生长控制。
Pub Date : 1976-01-01
N Bruchovsky, B Lesser

Growth of a normal androgen-responsive organ appears to be ordered by the function of three constraint mechanisms which are sensitive to the intranuclear concentration of androgens. For the complete expression of these constraint mechanisms, several properties underlying hormonal responsiveness must be manifest by the cell, including the presence of cytoplasmic receptor, the ability to transfer androgens into the nucleus, the competence to form nuclear receptor, and the fidelity of the interaction between androgens and chromatin. Cytoplasmic receptor alone is not an exclusive indication of hormonal dependence in vivo, but its presence is associated with enhanced ability of the cell to incoropate androgens into the nucleus. Androgens are required for the initiation of DNA synthesis and cell proliferation, and nuclear receptor may not be required for these responses. On the other hand, it is possible that the function of the latter molecule is concerned with negative feedback or cellular autolysis.

一个正常的雄激素反应器官的生长似乎是由三个对核内雄激素浓度敏感的约束机制的功能所决定的。为了完整地表达这些约束机制,细胞必须表现出激素反应的几个特性,包括细胞质受体的存在,将雄激素转移到细胞核的能力,形成核受体的能力,以及雄激素与染色质之间相互作用的保真度。细胞质受体本身并不是体内激素依赖性的唯一指标,但其存在与细胞将雄激素纳入细胞核的能力增强有关。雄性激素是DNA合成和细胞增殖起始所必需的,而核受体可能不需要这些反应。另一方面,后者分子的功能可能与负反馈或细胞自溶有关。
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引用次数: 0
Target sites for suppressing fertility in the male. 抑制男性生育能力的靶点。
Pub Date : 1976-01-01
M R Prasad, M Rajalakshmi

The present status and perspectives in the control of fertility in the male have been reviewed. There are two potential sites in the male reproductive processes that can be used as targets for regulation of fertility in the male: (1) inhibition of spermatogenesis, and (2) interference with sperm maturation in the epididymis. A variety of compounds tested for their antispermatogenic action in laboratory animals have no future for the control of fertility in the human male because of a number of undesirable side effects (cf. Prasad, 1973). Progestational compounds inhibit spermatogenesis by affecting the hypothalamo-hypophysial system and result in impairment of libido. The possibility of adjustment of the minimal dose of progestational compounds required to induce suppression of spermatogenesis and reduction of plasma testosterone to a level compatible with the maintenance of normalcy of libido and potency needs to be studied. A new approach to contraception in the male involves the use of a combination of progestational compounds for suppression of spermatogenesis along with testosterone (administered through silastic capsule implants or as intramuscular injections) for maintenance of libido and accessory sex gland function. A number of such combinations have been tested clinically with some success. However, the limitations of side effects, such as weight gain, gynecomastia, and psychological complications preclude their long-term use for contraception in man. Short-term use of these combination regimens by the male for 1 year followed by use of a contraceptive method by the female may be desirable to encourage partnership in family planning. Although testosterone and other androgens suppress spermatogenesis in man, the feasibility of their use for contraception depends on the establishment of a dosage and mode of adminstration that provide antispermatogenic action without causing more general metabolic alterations. Inhibition of spermatogenesis by selective interference with the action of FSH on the Sertoli cells by active or passive immunization or by selective suppression of synthesis and release of FSH by administration of "Inhibin" offers exciting possibilities in the control of fertility in the male. Studies on the physiology of the rete testis highlight its importance as a post-tubular site of action of antifertility agents in conveying (to the epididymis) compounds interfering with epididymal functions and/or viability of spermatozoa. A new approach to the induction of functional sterility in the male by selective alteration of epididymal function by a local androgen deprivation effect has been successfully tested in clinical trials. Small doses of cyproterone acetate, administered orally, result in maintenance of libido and accessory sex gland function accompanied by a decrease in the motility of ejaculated spermatozoa and incomplete inhibition of spermatogenesis...

综述了男性生育控制的研究现状和前景。在男性生殖过程中,有两个潜在的位点可以作为男性生育调节的靶点:(1)抑制精子发生,(2)干扰附睾中的精子成熟。在实验动物身上测试的各种化合物的抗生精作用,由于许多不良的副作用,在控制人类男性的生育能力方面没有前途(cf. Prasad, 1973)。孕激素化合物通过影响下丘脑-垂体系统抑制精子发生,导致性欲受损。需要研究调节诱导抑制精子发生和血浆睾酮降低到与维持正常性欲和效力相容的水平所需的孕激素化合物的最小剂量的可能性。一种新的男性避孕方法是结合使用孕激素化合物来抑制精子发生,同时使用睾酮(通过硅胶胶囊植入或肌肉注射)来维持性欲和副性腺功能。许多这样的组合已经在临床试验中取得了一些成功。然而,副作用的局限性,如体重增加、男性乳房发育症和心理并发症,使其无法长期用于男性避孕。为了鼓励计划生育中的伙伴关系,男性短期使用这些联合方案1年,然后女性使用一种避孕方法可能是可取的。尽管睾酮和其他雄激素抑制男性的精子生成,但它们用于避孕的可行性取决于确定的剂量和给药方式,既能提供抗精子生成的作用,又不会引起更普遍的代谢改变。通过主动或被动免疫选择性地干扰卵泡刺激素对支持细胞的作用,或通过给予抑制素选择性地抑制卵泡刺激素的合成和释放,从而抑制精子发生,这为控制男性的生育能力提供了令人兴奋的可能性。对睾丸网生理学的研究强调了它作为抗生育药物在输送(到附睾)干扰附睾功能和/或精子活力的化合物时的管后作用部位的重要性。一种通过局部雄激素剥夺效应选择性改变附睾功能来诱导男性功能性不育的新方法已经成功地在临床试验中得到验证。口服小剂量醋酸环丙孕酮,可维持性欲和辅助性腺功能,同时降低射精精子的运动能力和不完全抑制精子发生。
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引用次数: 0
Prolactin influences upon androgen action in male accessory sex organs. 催乳素对男性副性器官雄激素作用的影响。
Pub Date : 1976-01-01
J A Thomas, E J Keenan

The hormones of the pituitary gland are capable of directly influencing the function of male accessory sex organs. Among these hormones, prolactin in particular has been observed to enhance consistently the effects of androgens in the prostate gland and/or the seminal vesicles of rats, mice, and guinea pigs as well as in the accessory sex organs of other species. Prolactin-mediated augmentation of testosterone's effects upon these tissues is related primarily to the growth-promoting influences of this steroid. However, under certain experimental conditions, the androgen-dependent production of secretions by these organs has also been enhanced by prolactin treatment. Studies in the mouse have indicated that prolactin primarily enhances the proliferative phase of androgen action in male accessory sex tissues. Testosterone stimulation of RNA synthesis was unaffected by simultaneous administration of prolactin. The mechanism by which prolactin causes enhanced androgen responses in the prostate gland and seminal vesicles is not well understood. It would appear, however, that prolactin neither stimulates increased accumulation of androgen into the accessory sex organs, nor does it enhance the conversion of testosterone to the more "active" androgen, dihydrotestosterone. The effects of prolactin on these tissues are, however, dependent upon the presence of dihydrotestosterone. Uncertain, at present, are the possible effects of prolactin on the binding or retention of androgens (dihydrotestosterone?) in the prostate gland or in the seminal vesicles. There is evidence that hypophysectomy reduces the nuclear binding of dihydrotestosterone in the cells of the prostate gland. Perhaps prolactin is a pituitary factor(s) which is important in regulating nuclear binding of dihydrotestosterone in male accessory sex organs. The direct influences of prolactin upon androgen action in the cells of the accessory sex organs may involve several sites of action (Figure 2). For example, it is currently understood that when testosterone enters the cell cytoplasm it is subsequently converted to the more "active" androgen, dihydrotestosterone (DHT), by reduction at the 5alpha position. Dihydrotestosterone is then either bound to a cytoplasmic "receptor" protein (Rc) or is further metabolized to either 5alpha-androstane-3alpha,17beta-diol or 5alpha-androstane-3beta,17beta-diol (DIOL). The binding of DHT to its cytoplasmic receptor protein results in translocation of the steroid-receptor complex into the nucleus where presumably the complex dissociates and DHT exerts its androgenic effects. The transport of DHT to the nucleus can also result from the conversion of testosterone to DHT by nuclear membrane-bound 5alpha-reductase. Prolactin augmentation of DHT effects is envisioned as resulting from interaction of prolactin with its receptor, which due to the large size of the prolactin molecule is probably located in or on the plasma membrane...

垂体激素能直接影响男性副性器官的功能。在这些激素中,泌乳素已被观察到持续增强雄激素在大鼠、小鼠和豚鼠的前列腺和/或精囊以及其他物种的辅助性器官中的作用。催乳素介导的睾酮对这些组织作用的增强主要与这种类固醇的促生长作用有关。然而,在某些实验条件下,这些器官的雄激素依赖性分泌物的产生也通过催乳素治疗得到增强。小鼠研究表明,催乳素主要增强雄性副性组织中雄激素的增殖期作用。睾酮刺激RNA合成不受同时给药催乳素的影响。催乳素引起前列腺和精囊雄激素反应增强的机制尚不清楚。然而,看起来,催乳素既不会刺激雄激素向附属性器官的积累,也不会促进睾酮向更“活跃”的雄激素——双氢睾酮的转化。然而,催乳素对这些组织的影响取决于双氢睾酮的存在。目前尚不清楚催乳素对雄激素(双氢睾酮?)在前列腺或精囊中的结合或保留的可能影响。有证据表明垂体切除术减少了前列腺细胞中双氢睾酮的核结合。也许催乳素是一种垂体因子,在调节男性副性器官中双氢睾酮的核结合中起重要作用。催乳素对辅助性器官细胞中雄激素作用的直接影响可能涉及几个作用位点(图2)。例如,目前人们了解,当睾酮进入细胞质后,它随后通过5 α位置的还原转化为更“活跃”的雄激素——双氢睾酮(DHT)。然后,双氢睾酮要么与细胞质“受体”蛋白(Rc)结合,要么进一步代谢为5 -雄烷-3 - α,17 - β -二醇或5 -雄烷-3 - β,17 - β -二醇(DIOL)。二氢睾酮与其细胞质受体蛋白的结合导致类固醇受体复合体易位进入细胞核,复合体可能在细胞核中解离,二氢睾酮发挥其雄激素作用。二氢睾酮转运到细胞核也可以通过核膜结合的5 -还原酶将睾酮转化为二氢睾酮。催乳素增强DHT的作用被认为是由于催乳素与其受体的相互作用,由于催乳素分子的大尺寸可能位于或位于质膜上…
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引用次数: 0
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Advances in sex hormone research
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