Clinics in Endocrinology and Metabolism最新文献

{"title":"9 Pilosebaceous physiology in relation to hirsutism and acne","authors":"Robert L. Rosenfield","doi":"10.1016/S0300-595X(86)80029-9","DOIUrl":"10.1016/S0300-595X(86)80029-9","url":null,"abstract":"<div><p>PSAs, with few exceptions, consist of a piliary and a sebaceous component. In androgen-sensitive areas, each has the capacity to develop into either a terminal hair follicle or a sebaceous follicle depending upon its location. Without androgen, there is no development of the sexual hair follicle or sebaceous gland. Androgens appear to promote sexual hair growth by recruiting a population of PSAs that have preset genetic sensitivity to initiate the production of terminal hairs. The site of action of androgens within the PSA is unclear. There are indications that androgens may act at more than one site in a system that requires two-way reciprocal interaction between dermal and epithelial cells for the generation of hair growth. Growth hormone appears to exert an important synergism with androgen in affecting the PSA, seemingly through the mediation of insulin-like growth factors.</p><p>Hirsutism is due to an increased density of growing terminal hairs. The majority of cases of moderately severe hirsutism in women are due to hyperandrogenaemia, as are half the cases of mild hirsutism and about one-quarter of the cases of mild acne vulgaris. We advocate reserving the term idiopathic hirsutism or idiopathic acne for those patients in whom excessive growth of terminal hair or acne is not explained by androgen excess. We believe that highly variable sensitivity to androgen within the population explains both idiopathic hirsutism and cryptic hyperandrogenaemia; that is, these disorders lie at opposite ends of the normal spectrum of sensitivity to androgen. The biological basis for the variations in responsiveness of PSAs to androgens is unknown. The regression of hirsutism induced by antiandrogen treatment is characterized by the growth of hairs that are more vellus in character, i.e. smaller and less medullated.</p></div>","PeriodicalId":10454,"journal":{"name":"Clinics in Endocrinology and Metabolism","volume":"15 2","pages":"Pages 341-362"},"PeriodicalIF":0.0,"publicationDate":"1986-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0300-595X(86)80029-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14076439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"4 Serum bioavailability of sex steroid hormones","authors":"William M. Pardridge","doi":"10.1016/S0300-595X(86)80024-X","DOIUrl":"10.1016/S0300-595X(86)80024-X","url":null,"abstract":"<div><p>This chapter has reviewed the factors underlying the transport of testosterone and oestradiol into tissues in vivo. The following points have been emphasized. (1) Albumin-bound testosterone is nearly freely available for transport into brain and liver and is partially available for transport into salivary gland and lymph node; testosterone transport into hair follicles has not been measured thus far.</p><p>(2) SHBG-bound testosterone is not available for transport into tissues; SHBG-bound oestradiol is available for transport into liver, salivary gland, and lymph node, but not into brain under normal conditions.</p><p>(3) The transport of hormone from the circulating plasma protein-bound pool involves tissue-mediated enhanced dissociation of the hormone from the protein without significant exodus of the plasma protein from the microcirculation compartment. The tissue-mediated enhanced dissociation mechanism varies in activity between different organs and is a much more important factor than organ differences in capillary transit times in regulating the amplification of hormone delivery to different tissues.</p><p>(4) The concentration of free testosterone inside cells in the absence of significant cellular metabolism of the hormone is nearly ten times greater than the concentration of free testosterone in vitro, but is nearly equal to the concentration of free plus albumin-bound hormone.</p><p>(5) In the presence of active tissue metabolism of hormone, the concentration of cellular free testosterone may be much less than the albumin-bound hormone and may fortuitously approximate the concentration of free testosterone in vitro. This is the situation in salivary gland; the low concentration of testosterone in saliva appears to be due to active salivary metabolism of the hormone, since both free and albumin-bound testosterone are available for transport into salivary gland.</p></div>","PeriodicalId":10454,"journal":{"name":"Clinics in Endocrinology and Metabolism","volume":"15 2","pages":"Pages 259-278"},"PeriodicalIF":0.0,"publicationDate":"1986-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0300-595X(86)80024-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14645552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3 Changing concepts of active androgens in blood","authors":"Pentti K. Siiteri,&nbsp;Niklas H. Simberg","doi":"10.1016/S0300-595X(86)80023-8","DOIUrl":"10.1016/S0300-595X(86)80023-8","url":null,"abstract":"<div><p>We have provided a brief historical review of developments in our understanding of the endocrine mechanisms underlying the expression of androgen action in women. An alternative to the free hormone concept is considered which proposes that, at least in some target cells, androgens bound to SHBG are the biologically relevant molecules. In nearly every instance, the changes in blood levels of SHBG that have been observed are consistent with this idea. At present there are only bits of direct evidence to support the hypothetical mechanism proposed. As already mentioned, control of androgen action at the level of cellular uptake would provide obvious advantages as well as a potential mechanism to explain the antagonism between androgens and oestrogens which is still a mystery. It is important to note that the proposed mechanism is not obligatory for androgen or other steroid hormone action. Synthetic steroids which do not bind to SHBG or CBG clearly can gain access to target cells by simple diffusion and bind to intracellular receptors. Compounds such as methyltestosterone and dexamethasone are metabolized much more slowly than their natural counterparts and therefore are cleared slowly from the circulation. It is possible that the well-known difficulties in selecting appropriate therapeutic regimens with such compounds is related to the fact that they bypass an important regulatory step in steroid hormone action—modulated entry into target cells. Hopefully, the recent development of powerful new tools of molecular endocrinology will hasten the answer to the question: What is the active androgen in blood?</p></div>","PeriodicalId":10454,"journal":{"name":"Clinics in Endocrinology and Metabolism","volume":"15 2","pages":"Pages 247-258"},"PeriodicalIF":0.0,"publicationDate":"1986-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0300-595X(86)80023-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14645551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"10 Treatment of hirsutism with spironolactone","authors":"Roland R. Tremblay","doi":"10.1016/S0300-595X(86)80030-5","DOIUrl":"10.1016/S0300-595X(86)80030-5","url":null,"abstract":"<div><p>The discovery of compounds possessing antiandrogenic activities has led to their utilization in the treatment of hirsutism of various aetiologies. Spironolactone generally lowers the plasma testosterone by altering its formation and metabolism as well as by decreasing its blood production rate; the medication also contributes to increase the peripheral conversion of testosterone to oestradiol. A major action is that spironolactone inhibits androgen binding to receptor molecules in the cytosol or the nucleus of target tissues such as the skin. During the last five years, we have studied over 450 cases of hirsutism. Approximately 80% of these women were treated with spironolactone alone or in association with dexamethasone (2.5%) or an oral contraceptive (15%). Hirsutism was classified according to <span>Lorenzo (1970)</span>. Good to very good clinical results were observed in 80% of the patients who were under study for a minimum of 3 to 4 years. Adverse side-effects were recorded in less than 5% of our group of patients. On the basis of our data and our clinical experience, we conclude that spironolactone is an effective drug in the treatment of female hirsutism.</p></div>","PeriodicalId":10454,"journal":{"name":"Clinics in Endocrinology and Metabolism","volume":"15 2","pages":"Pages 363-371"},"PeriodicalIF":0.0,"publicationDate":"1986-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0300-595X(86)80030-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14076071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1 Adrenal and gonadal androgen secretion in normal females","authors":"Christopher Longcope","doi":"10.1016/S0300-595X(86)80021-4","DOIUrl":"10.1016/S0300-595X(86)80021-4","url":null,"abstract":"<div><p>Both the adrenal and the ovary contain the biosynthetic pathways necessary for androgen synthesis and secretion. The fetal ovary is not very active but the fetal adrenal is an important source of DHAS. However the secretion of DHAS declines markedly after birth and until puberty there is little androgen secretion by either the adrenal or the ovary.</p><p>Post-pubertally, the adrenal secretes DHAS, DHA, Δ⁴-A and T from the reticularis and probably the fasciculata. This secretion is under ACTH control, at least in part, but apparently also under control of another pituitary polypeptide tentatively called ‘adrenal androgen secretory hormone’. The adrenal secretion rates are in the range of 7–14 mg/day for DHAS, 3–4 mg/day for DHA, 1–1.5 mg/day for Δ⁴-A and 50 μg/day for T.</p><p>Androgen secretion from the ovary arises in part from the theca cells of the follicle, the corpus luteum and the stromal cells, under LH control, and will vary somewhat during the normal menstrual cycle. The ovarian secretion rate in the follicular phase is 1–2 mg/day for DHA, 1–1.5 mg/day for Δ⁴-A and about 50 <em>μ</em>g/day for T. In the peri-ovulatory period the secretion rate of Δ⁴-A can rise to 3–3.5 mg/day but there appears to be little change in the secretion of DHA and T. The normal ovary does not secrete significant amounts of DHAS.</p><p>In about 50% of post-menopausal women the ovaries continue to secrete some T but little Δ⁴-A or DHA.</p></div>","PeriodicalId":10454,"journal":{"name":"Clinics in Endocrinology and Metabolism","volume":"15 2","pages":"Pages 213-228"},"PeriodicalIF":0.0,"publicationDate":"1986-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0300-595X(86)80021-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14146881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"7 Regulation of androgen receptor and 5α-reductase in the skin of normal and hirsute women","authors":"Pierre Mauvais-Jarvis","doi":"10.1016/S0300-595X(86)80027-5","DOIUrl":"10.1016/S0300-595X(86)80027-5","url":null,"abstract":"<div><p>The hormonal activity of androgens is mediated in target cells, particularly in human skin, by two kinds of proteins: the androgen receptor and the enzyme 5α-reductase. In well differentiated androgen target cells, 5α-reductase achieves the transformation of testosterone (T) into dihydrotestosterone (DHT), a more active androgen than T, because of its higher affinity for the receptor. In other words, 5α-reductase acts as an amplifier of the androgen signal but is not absolutely required for androgen action. Regarding the regulation of the androgen receptor, minimal information is available. However, in genital skin, the receptor seems to be predominantly localized in the cytosolic compartment before puberty in males and in the nuclear compartment after puberty. In hirsute patients, recent data on genital skin fibroblasts do not show significant differences between the binding capacity of fibroblasts from normal and hirsute women whereas there is no difference between normal men and women.</p><p>5α-Reductase activity seems to be a very important step in the processes involved in androgen action. While 5α-reductase activity present in the skin of external genitalia does not seem to be androgen dependent, this is not the case for the enzyme located in pubic skin. In this area, a sex difference between males and females may be observed both in skin homogenates and in cultured fibroblasts. In addition DHT added to a medium of pubic skin fibroblasts is capable of increasing 5α-reductase activity. This increase is not observed when cyproterone acetate is added to the medium and in patients with testicular feminization syndrome without receptors. Pubic 5α-reductase activity is an androgen receptor mediated phenomenon. In patients with hirsutism, and particularly idiopathic hirsutism, 5α-reductase activity is high without an increase in circulating androgens. This may be observed both in pubic skin homogenates and in cultured fibroblasts. Thus, an excess of skin 5α-reductase activity may be considered as a cause of hirsutism but both the exact level of the abnormality in the regulation of the enzyme and its genetic control remain to be elucidated.</p></div>","PeriodicalId":10454,"journal":{"name":"Clinics in Endocrinology and Metabolism","volume":"15 2","pages":"Pages 307-317"},"PeriodicalIF":0.0,"publicationDate":"1986-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0300-595X(86)80027-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14076438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"12 Treatment of hirsutism with 5α-reductase inhibitors","authors":"J.R. Brooks","doi":"10.1016/S0300-595X(86)80032-9","DOIUrl":"10.1016/S0300-595X(86)80032-9","url":null,"abstract":"<div><p>Much of the evidence gathered from studies of 5α-reductase activity levels and androgen metabolism in the skin of hirsute women and the excretion of androgen metabolites by hirsute women indicates that 5α-reduced androgens are probably of primary importance in hirsutism. Unfortunately, until very recently, the lack of a suitable 5α-reductase inhibitor made it very difficult to adequately test the hypothesis that such an inhibitor might be useful in the treatment of hirsutism and certain other androgen-related diseases. No substance was available which had good, unambiguous activity in vivo as a 5α-reductase inhibitor.</p><p>A number of 4-azasteroids have now been found to possess excellent 5α-reductase inhibitory activity both in vitro and in vivo. Among other properties, several of these compounds show little or no affinity for the androgen receptor of rat prostate cytosol, they attenuate the growth promoting effect of T, but not DHT, on the ventral prostate of castrated male rats, they cause a marked reduction in prostatic DHT concentration in acutely treated rats and dogs and they bring about a significant decline in prostate size in chronically treated rats and dogs. It is expected that, in the near future, one or more of these highly active 5α-reductase inhibitors will be tested in the clinic as a treatment for hirsutism. The results of those studies will be awaited with a great deal of interest since they should considerably advance our understanding of this disease and possibly contribute to its control.</p></div>","PeriodicalId":10454,"journal":{"name":"Clinics in Endocrinology and Metabolism","volume":"15 2","pages":"Pages 391-405"},"PeriodicalIF":0.0,"publicationDate":"1986-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0300-595X(86)80032-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14645556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Index","authors":"","doi":"10.1016/S0300-595X(86)80033-0","DOIUrl":"https://doi.org/10.1016/S0300-595X(86)80033-0","url":null,"abstract":"","PeriodicalId":10454,"journal":{"name":"Clinics in Endocrinology and Metabolism","volume":"15 2","pages":"Pages 407-409"},"PeriodicalIF":0.0,"publicationDate":"1986-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0300-595X(86)80033-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138246339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6 Peripheral androgens and the role of androstanediol glucuronide","authors":"Richard Horton,&nbsp;Roger Lobo","doi":"10.1016/S0300-595X(86)80026-3","DOIUrl":"10.1016/S0300-595X(86)80026-3","url":null,"abstract":"","PeriodicalId":10454,"journal":{"name":"Clinics in Endocrinology and Metabolism","volume":"15 2","pages":"Pages 293-306"},"PeriodicalIF":0.0,"publicationDate":"1986-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0300-595X(86)80026-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14645554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"10 Paracrine control of the testis","authors":"Richard M. Sharpe","doi":"10.1016/S0300-595X(86)80049-4","DOIUrl":"10.1016/S0300-595X(86)80049-4","url":null,"abstract":"<div><p>The mammalian testis is under the overall control of pituitary gonadotropins but the utilization of these signals to achieve normal testicular function involves complex local interactions between the Sertoli and germ cells, the Sertoli and peritubular cells, and the Sertoli and Leydig cells as well as local control of the testicular vasculature. These interactions serve two purposes: (1) to coordinate the functions of the three testicular compartments (seminiferous tubules, interstitium and the vasculature); and (2) to control the complex but orderly sequence of events that constitutes the spermatogenic cycle. This process, which involves multiplication, differentiation and translocation of the germ cells is organized into a sequence of stages, each of which is composed of a constant association of germ cells at four or five different stages of development. At each stage of the spermatogenic cycle, different events occur and the function of the Sertoli cells alters, probably in accordance with the changing requirements of the associated germ cells. As yet, our understanding of these many local events is extremely limited, particularly with respect to the identity of the hormones/factors involved in controlling the various processes.</p><p>Our knowledge of paracrine control mechanisms in the testis is derived mainly from studies of the rat, but as the process of spermatogenesis is essentially the same in most mammals and involves the same sequence of events, then findings in the rat can probably be applied in general, if not in detail, to the human testis; the limited direct information available on the human testis supports this view. As most cases of infertility in men occur despite normal or raised serum gonadotropin levels and are characterized by the production of reduced or normal numbers of sperm, then it seems likely that malfunction of one or more of the intricate paracrine processes within the testis may be involved in the aetiology of idiopathic oligospermia. It is therefore argued that advances in our knowledge of the paracrine control of the testis should have major repercussions on our ability to understand, and eventually treat, idiopathic infertility in men, and also to induce infertility for contraceptive purposes.</p></div>","PeriodicalId":10454,"journal":{"name":"Clinics in Endocrinology and Metabolism","volume":"15 1","pages":"Pages 185-207"},"PeriodicalIF":0.0,"publicationDate":"1986-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0300-595X(86)80049-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14637426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}