Endocrinology of sex steroid hormones and cell dynamics in the periodontium (original) (raw)
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Androgens, anti-androgens and anabolic steroids
Androgens are steroid hormones that are secreted primarily by the testis, and testosterone is the principal androgen secreted. Its primary function is to regulate the differentiation and secretory function of male sex accessory organs. Androgens also possess protein anabolic activity that is manifested in skeletal muscle, bone, and kidneys. As a class, androgens are reasonably safe drugs, having limited and relatively predictable side effects. CHEMISTRY AND BIOSYNTHESIS The basic structure of all steroid hormones is similar (see Chapter 60, Fig. 60.4). The addition of a hydrogen atom at position 5 and an angular methyl group at positions 18 and 19 establishes the basic chemical framework for androgenic activity. CHARACTERIZATION OF PLASMA ANDROGENS In males, testosterone is the principal circulating androgen, and the testes are the principal source. Although the adrenals are capable of androgen synthesis, less than 10% of the circulating androgens in men are produced in the adrenals. Testosterone is synthesized by Leydig cells of the testes at the rate of about 8 mg/24 hours, providing a plasma concentration of 0.5 to 0.6 g/dL. In females, the ovaries contribute approximately one-third of the total androgens synthesized, while the adrenals contribute the rest. Androstenedione, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEA-S) are other mildly androgenic compounds of secondary importance in males and females. The gonads and the adrenal cortex are capable of secreting androstenedione
Toxicological Sciences, 2011
Anabolic androgenic steroids (AAS) are testosterone derivatives originally designed to enhance muscular mass and used for the treatment of many clinical conditions as well as in contraception. Despite popular interest and abuse, we still lack a broad understanding of effects of AAS on synthesis of steroid hormones on the molecular level. This study was designed to systematically analyze the effects of pharmacological/high doses of testosterone on steroidogenic machinery in Leydig cells. Two different experimental approaches were used: (1) In vivo experiment on groups of adult male rats treated with testosterone for 1 day, 2 weeks, and 2 months; (2) Direct in vitro testosterone treatment of Leydig cells isolated from intact rats. Result showed that prolonged in vivo treatment with testosterone decreased the expression of Scarb1 (scavenger receptor class B type 1), Tspo (translocator protein), Star (steroidogenic acute regulatory protein), Cyp11a1 (cholesterol side-chain cleavage enzyme), and Cyp17a1 (17a-hydroxylase/17, 20 lyase) in Leydig cells. Oppositely, the expression of Hsd3b (3-beta-hydroxysteroid dehydrogenase/delta-5-delta-4 isomerase), Ar (androgen receptor), and Pde4a/b (cyclic adenosine monophosphate-dependent phosphodiesterases) was increased. Androgenization for 2 weeks inhibited Cyp19 (aromatase) transcription, whereas 2-month exposure caused the opposite effect. Direct in vitro testosterone treatment also decreased the expression of Cyp11a1, Cyp17a1, and Cyp19a1, whereas Hsd3b was upregulated. The results of expression analysis were supported by declined steroidogenic capacity and activity of Leydig cells, although conversion of pregnenolone to progesterone was stimulated. The upregulation of AR and 3bHSD in testosterone-impaired Leydig cells steroidogenesis could be the possible mechanism that maintain and prevent loss of steroidogenic function.
Androgen metabolism in relation to growth stimulation by a uterine cell line
Molecular and Cellular Endocrinology, 1977
The metabolism of radioactive testosterone, 5cr-dihydrotestosterone, 4-androstene-3@,17fldiol or 4-androstene-3cu,lIlp-diol by the human cell line NHIK 3025, derived from a carcinoma of the uterine cervix, was studied. The cells were grown in Eagle's minimal essential medium (MEM) with a steroid concentration of 10e7 M for 4 days. Androgen metabolism by this cell line is essentially the same as for other androgen-responsive cells. The most interesting testosterone metabolite in this system is 4-androstene-3&17pdiol, and the separation of this compound from 4-androstene-3o,l7pdiol and the two corresponding So-reduced diols is described. Since 4-androstene-3p,l7pdiol
Sex steroid hormones and cell dynamics in the periodontium
Critical Reviews in Oral Biology & Medicine, 1994
The biological changes that occur in tissues of the periodontium during puberty, the menstrual cycle, pregnancy, menopause, and oral contraceptive use have heightened interest in the relationship between sex steroid hormones and periodontal health. These clinical observations coupled with tissue specificity of hormone localization, identification of hormone receptors, as well as the metabolism of hormones have strongly suggested that periodontal tissues are targets for androgens, estrogens, and progestins. The etiologies of periodontal endocrinopathies are diverse; nonetheless, periodontal pathologies may be a consequence of the actions and interactions of sex steroid hormones on specific cells found in the periodontium.
Androgens and androgen receptor: Above and beyond
Molecular and Cellular Endocrinology, 2018
The role of androgens in male development and reproductive function have been well described for nearly 100 years. The identification and isolation of testosterone in the early part of the last century, coupled with the cloning of the cDNA for the androgen receptor (AR) in the late 20th century nicely book end the basis for the molecular understanding of androgen action. Now in the 21st century, the wider impact of androgenic steroids outside classical male reproductive tissues is gaining prominence. Four areas of particular importance are evident: (1) the recognition of testosterone as a 'Goldilocks' molecule, with too little or too much disrupting normal cellular homeostasis; (2) evidence for dynamic, tissue-specific regulation of androgen biosynthesis and metabolism (3) an increased appreciation of the role of androgens in female reproductive tissues and (4) a role for androgens in regulating non-reproductive tissues in both men and women (Fig. 1). To address these new and emerging roles in this special issue we have brought together 12 state-of-the art reviews from leading researchers which demonstrate current knowledge and highlight unresolved questions and future research directions. The main circulating androgen, testosterone (T) is primarily synthesized in the gonads (testes and ovaries) and this can be converted to the more potent androgenic steroid 5adihydrotestosterone (DHT) or the oestrogen, 17b-oestradiol (E 2) (Fig. 1). The less potent, but significant androgen, dehydrepiandrosterone (DHEA) and its sulphated metabolite (DHEA-S) are present in far higher concentrations in blood that bathes peripheral organs than that of T or DHT. It is therefore timely to consider the balance between biosynthesis and metabolism in controlling circulating and tissue levels of active androgenic steroids which can exert effects on tissues expressing AR. Schiffer et al. (2017) discuss our current understanding of the importance of intracrine androgen biosynthesis and metabolism together with hepatic metabolism and excretion steroids. In a comprehensive review they describe the expression of steroidogenic enzymes in involved in both de novo and tissue-selective 'back door' pathway of androgen biosynthesis. The actions of T and DHT are mediated primarily though binding to the androgen receptor (AR) a member of the nuclear receptor superfamily of ligand-activated transcription factors (Fig. 1). The AR gene is located on the long arm of the X-chromosome and therefore males are hemizygous, while X-inactivation in females results in one active copy of the gene. The AR gene lacks a TATA-box in the promoter and transcription is driven by protein specificity factor 1 (Sp1). Interestingly, the expression of the receptor gene is autoregulated by androgens and both up-and down-regulation has been observed. Intriguingly this may be cell-type specific. Hunter et al. (2017) discuss the molecular pathways regulating AR mRNA and protein levels in different cell types. Understanding more fully
1985
The relative potencies of testosterone (T), testosterone propionate (TP) and other related steroids (Sa-dihydrotestosterone, DHT; 5a-androstane-3ql7/?-diol, z-dial; 5a-androstane-3p,17p-diol, b-dial) in restoring some morphological and functional characteristics of submandibular gland (SMG) were investigated in castrated mice. The steroids restored to near-control values the glandular weight and total protein content, a-diol and TP being the most effective compounds tested; with regard to proteolytic activity stimulal.ion, fi-diol was more effective than DHT. The a-diol metabolite was unique in significantly increasing DNA synthesis. In competition studies, cc-diol and /?-diol were ineffective in displacing the specifically bound ['HI-R1881 from the SMG androgen-binding macromolecules. Thus T can elicit its effects on SMG without the need of prior conversion to DHT; there must be alternative, receptorindependent mechanisms whereby r-and p-diol exert trophic/metabolic effects on murine SMG.
Acta Endocrinologica, 1980
Homogenates of normal or cryptorchid, human testes were incubated with [3H]testosterone and a NADPH-generating system. [3H]4-andostene,7\g=a\,17\ g=b\-di ol \ x=req-\ 3-one (7\g=a\-OH-testosterone)was isolated and identified from such incubations. To our knowledge this is the first demonstration that 7\g=a\-OH-testosteroneis a metabolite of testosterone in the human testis. 4-Andro-stene,6\g=b\,17\g=b\\x=req-\ diol-3-one (6\g=b\-OH-testosterone) and 4-androstene, 16\ g=a\ , 17\ g=b\ \ x=r eq-\ diol-3-one (16\g=a\-OH-testosterone) were also identified as testosterone metabolites. The specific activity of both testosterone 6\g=b\-and 16\g=a\-hydroxylase was higher than that of 7\g=a\-hydroxylase.Pre-pubertal or cryptorchid human testis tissues seem in our study to have higher testosterone 6\g=b\and 7\g=a\-hydroxylase activity than normal
Testosterone Production in Vitro in Human Testicular Tissue
Andrologia, 2009
The biosynthesis of testosterone within the testis has been shown to take place along different metabolic pathways in different species. In the testis from elderly men with prostatic carcinoma the AS-metabolic pathway has been shown to be preferred. Less is known about the preferred pathway in younger adults. In this study, testicular biopsy specimens from 33 adults (ranging from 27 to 35 years of age) were incubated with both tritiated pregnenolone and progesterone. The production of testosterone from these precursors was determined in vitro and was found to be significantly higher from pregnenolone than from progesterone, This indicates that pregnenolone was initially mainly converted along the AS-metabolic pathway to 17ahydroxypregnenolone and probably further to dehydroepiandrosterone before it was subsequently transformed to a A4-metabolite. Similar results were obtained in incubation studies performed with testicular tissue from eleven elderly men (ranging from 60 to 83 years of age). In conclusion, studies of the testosterone production in vitro suggest that the AS-metabolic pathway is preferred in the testis from younger as well as elderly men. Testosteronproduktion des Hodengewebes in vitro Zusammenfassung: Wie gezeigt wurde, verlauft die Testosteronbiosynthese in den Hoden bei verschiedenen Spezies uber unterschiedliche Metabolisierungswege. Es wurde dargelegt, da5 in den Hoden von alteren Mglnnern mit Prostata-Karzinom der Reaktionsweg iiber AS-Metabolite bevorzugt wird. a e r den Metabolisierungsweg in den Hoden jungerer Mannerist weniger bekannt. In dieser Studie wurden Hodenbiopsiepriiparate von 33 Mannem zwischen 27 und 35 Jahren in H-Pregnenolon und H-Progesteron inkubiert. Die Testosteronproduktion dieser Vorstufen wurde in vitro bestimmt und war bei Pregnenolon signifkant hoher gegenuber Progesteron. Dieses weist darauf hin, da5 Pregnenolon sich urspriinglich haupt-Gchlich iiber den AS-Metabolisierungsweg zu 17a-Hydroxapregnenolon und moglicherweise weiter zu Dehydroepiandrosteron umwandelt, bevor es SchlieBlich zu einem A4-Metaboliten transformiert wird. julnliche Resultate wurden bei Inkubationsstudien von Hodengewebe von 1 1 iilteren Miinnem zwischen 60 und 83 Jahren erzielt.