From 41ce92781168f13b7f8509c79ff4fd96bde8a5a8 Mon Sep 17 00:00:00 2001 From: darrenieh26863 Date: Thu, 2 Apr 2026 21:45:03 +0800 Subject: [PATCH] Add Testosterone: a metabolic hormone in health and disease --- ...ne%3A-a-metabolic-hormone-in-health-and-disease.md | 11 +++++++++++ 1 file changed, 11 insertions(+) create mode 100644 Testosterone%3A-a-metabolic-hormone-in-health-and-disease.md diff --git a/Testosterone%3A-a-metabolic-hormone-in-health-and-disease.md b/Testosterone%3A-a-metabolic-hormone-in-health-and-disease.md new file mode 100644 index 0000000..94c4de5 --- /dev/null +++ b/Testosterone%3A-a-metabolic-hormone-in-health-and-disease.md @@ -0,0 +1,11 @@ +
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The Organon group in the Netherlands were the first to isolate the hormone, identified in a May 1935 paper "On Crystalline Male Hormone from Testicles (Testosterone)". Suffering the ridicule of his colleagues, he abandoned his work on the mechanisms and effects of androgens in human beings. Testosterone has been detected at variably higher and lower levels among men of various nations and from various backgrounds, explanations for the causes of this have been relatively diverse. In measurements of testosterone in blood samples, different assay techniques can yield different results. Several professional medical groups have recommended that 350 ng/dL generally be considered the minimum normal level, which is consistent with previous findings.non-primary source neededmedical citation needed Levels of testosterone in men decline with age. 5α-Reductase is highly expressed in the male reproductive organs (including the prostate gland, seminal vesicles, and epididymides), skin, hair follicles, and brain and aromatase is highly expressed in adipose tissue, bone, and the brain. +The kinetic parameters for testosterone 6β-hydroxylation have been previously determined for the recombinant CYP3A4, CYP3A5, and CYP3A7 enzymes (Williams et al., 2002), but the kinetic characteristics for the 2β-hydroxylation and 2α-hydroxylation, other predominant CYP3A metabolic oxidations, have not been thoroughly investigated. As a control to determine whether the initial docking parameters functioned appropriately, MDZ was redocked to the empty CYP3A4 receptor template (data not shown). Indeed, testosterone 6β-hydroxylation is a commonly used assay to characterize the CYP3A enzyme activity in a variety of test systems (Sohl et al., 2009). In silico docking studies revealed at least two different binding modes for [buy testosterone steroids](http://www.flop.jp.org/bbs_font/bbs.cgi) between CYP3A4 and CYP3A7. Interestingly, we found that the 2α-OH-T/6β-OH-T ratio varied with substrate concentration when [testosterone shop](https://hayatjadidagroups.com/employer/should-i-see-a-urologist-or-an-endocrinologist-for-low-testosterone/) was incubated with CYP3A7, suggesting that this ratio would likely not function well as a biomarker for CYP3A7 activity. The conversion of preg­nenolone to testosterone requires the action of 5-enzymes—(i) 3β-hydroxysteroid dehy­drogenase (3β-OHSD). Long recognized for its role as a sex hormone, mounting evidence underscores the importance of testosterone in the regulation of systemic metabolism in both male and female organisms. have been undertaken on the relationship between more general aggressive behavior, and feelings, and testosterone. Nearly all studies of juvenile delinquency and testosterone are not significant.|In the NOESY spectrum of WPS6, the presence of an NOE signal between H-1 and 19-CH3indicated that H-1 should be in a β-conformation (data not shown). 1H-NMR spectra of androsta-1,4-diene-3,17-dione and HPLC-purified steroid products (400 MHz, CDCl3). 13C-NMR chemical shifts for androsta-1,4-diene-3,17-dione compared to those of HPLC-purified steroid products in CDCl3 TLC, HPLC, UV absorption, and mass assignments of HPLC-purified products and the authentic compound androsta-1,4-diene-3,17-dionea The structures of WPS1 and WPS2 were identified by comparing their spectral data to assignments reported in the literature (34).|Prior to conducting the docking simulations with CYP3A4, the MDZ ligand was removed from the active site. In the case of CYP3A4, testosterone was docked into the active site of the ligand-free CYP3A4-midazolam (MDZ) crystal structure, as originally obtained by Sevrioukova and Poulos (2017) (Protein Data Bank ID code, 5TE8). The HLM incubation reactions (100 µl) were prepared similarly except that the concentration of testosterone was 50, 100, or 250 µM with 0.25 mg/ml microsomal protein, and the reactions were stopped after 20 minutes by the addition of ice-cold methanol (100 µl) containing 400 ng/ml 6β-hydrotestosterone-d3 (internal standard). The reactions were incubated for 10 minutes at 37°C under agitation and were stopped by the addition of ice-cold methanol (250 µl) containing 400 ng/ml 6β-hydrotestosterone-d3 (internal standard).|Likewise, testosterone is referred to as the male sex hormone for the roles it plays in male sexual development and function. Clinical trials demonstrate that testosterone replacement therapy improves the insulin resistance found in these conditions as well as glycaemic control and also reduces body fat mass, in particular truncal adiposity, cholesterol and triglycerides. One possible explanation for the shift in the regiospecificity of testosterone oxidation in CYP3A7 is that higher substrate concentrations increase the likelihood for multiple ligand binding to occur, and the multiple ligand–bound enzyme alters the orientation of testosterone within the active site, which leads to a shift in regiospecificity. The third, and least energetically favorable, binding pose obtained for CYP3A7 oriented the testosterone substrate in position for β-hydroxylation at the C2 atom (Fig. 7E). In conclusion, our data indicate an alternative binding mode for testosterone in CYP3A7 that favors the 2α-hydroxylation, suggesting significant structural differences in its active site compared with CYP3A4/5.|The 6β-hydroxylation of testosterone is catalyzed mainly by CYP3A4 and to a lesser extent CYP3A5 and is responsible for 75 to 80% of cytochrome P450-mediated testosterone metabolism. In the hepatic 17-ketosteroid pathway of testosterone metabolism, testosterone is converted in the liver by 5α-reductase and 5β-reductase into 5α-DHT and the inactive 5β-DHT, [thehrguardians.com](https://thehrguardians.com/employer/anger-hormones-cortisol-testosterone-and-adrenaline-explained/) respectively. An additional 40% of testosterone is metabolized in equal proportions into the 17-ketosteroids androsterone and etiocholanolone via the combined actions of 5α- and 5β-reductases, 3α-hydroxysteroid dehydrogenase, and 17β-HSD, in that order.|It is noteworthy that the hydration reaction at C-1/C-2 of steroids also occurred in the presence of molecular oxygen (data not shown), suggesting that the corresponding enzyme is not oxygen-labile. According to data from our previous work (5) and the present study, an outline for the initial reactions of a novel testosterone catabolic pathway is proposed using S. The presence of 1-testosterone-derived steroid intermediates in the samples was detected by ultraperformance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (UPLC-APCI-MS) as described below. In addition, because of their diverse physiological functions in the human body, steroid compounds may be ranked among the most widely marketed chemicals by the pharmaceutical industry (11).|Most steroid hormones present in the environment are produced by humans and livestock (25). The ring identification system (A to D) and carbon numbering system of steroids is as shown for testosterone. One of its derivatives, testosterone, belongs to the C19androgen group and is primarily secreted by the testes of males and ovaries of females.} +Here, a novel, oxygenase-independent testosterone catabolic pathway in such organisms is described. Since then, a variety of anaerobic bacteria have been described for the ability to degrade testosterone in the absence of oxygen. The oxic testosterone catabolic pathway involves several oxygen-dependent reactions and is not available for anaerobes. +Studies conducted in rats have indicated that their degree of sexual arousal is sensitive to reductions in testosterone. Testosterone levels follow a circadian rhythm that peaks early each day, regardless of sexual activity. Regular monitoring during treatment typically includes hematocrit levels every 3-6 months to prevent polycythemia, along with PSA monitoring in men over 40. Current clinical guidelines recommend comprehensive baseline evaluation including complete blood count, lipid panel, prostate-specific antigen, and cardiovascular risk assessment before initiating testosterone replacement therapy. Testosterone treatment for reasons other than possible improvement of sexual dysfunction may not be recommended. Serious side effects may include liver toxicity, heart disease (though a randomized trial found no evidence of major adverse cardiac events compared to placebo in men with low testosterone), and behavioral changes. It can be administered as a cream or transdermal patch that is applied to the skin, by injection into a muscle, as a tablet that is placed in the cheek, or by ingestion. +On the other hand, elevated testosterone in men may increase their generosity, primarily to attract a potential mate. Testosterone levels play a major role in risk-taking during financial decisions. This is particularly beneficial for humans since offspring are dependent on parents for extended periods of time and mothers have relatively short inter-birth intervals. Men who produce more testosterone are more likely to engage in extramarital sex. Men who produce less [buy testosterone cream](https://qarisound.com/brittnegrete9) are more likely to be in a relationship or married, and men who produce more testosterone are more likely to divorce. However, the testosterone changes observed do not seem to be maintained as relationships develop over time. There has been speculation that these changes in testosterone result in the temporary reduction of differences in behavior between the sexes. +This additional information could suggest, contrarily, that testosterone may encourage greed or selfishness. However men with high testosterone were significantly 27% less generous in an ultimatum game. Test subjects with an artificially enhanced [testosterone purchase](https://superocho.org/@sallyfallon84?page=about) level generally made better, fairer offers than those who received placebos, thus reducing the risk of a rejection of their offer to a minimum. For one study, subjects took part in a behavioral experiment where the distribution of a real amount of money was decided. In humans, testosterone appears more to promote status-seeking and social dominance than simply increasing physical aggression. Thus the link between [buy testosterone enanthate online](https://www.kingspalace.net/louveniateeter) and aggression and violence is due to these being rewarded with social status. +It only functions properly when you’re getting enough nutrients through foods like vegetables, fruits and lean meats. The anabolic hormones are responsible for growth and tissue repair. "It’s also the process involved in a child’s growth and in building stronger muscles." "One example of anabolism in action is when your body is trying to heal a cut. For example, it’s the process that dissolves a piece of bread into simple nutrients your body can use, like glucose (blood sugar). +The recombinant CYP3A incubation reactions (250 µl) contained various concentrations of testosterone (2.5–500 µM) that were dissolved in methanol (1% v/v); CYP3A4 (5 pmol/ml), CYP3A5 (20 pmol/ml), or CYP3A7 (50 pmol/ml) Supersomes; 100 mM potassium phosphate buffer (pH 7.4); and 3 mM MgCl2. Individual male fHLMs, lot numbers 5 (120 days estimated gestational age) and 18 (100 days estimated gestational age), were prepared as previously described (Shuster et al., 2014). Individual male HLMs, lot numbers DDV and RGS, were purchased from BioreclamationIVT (Hicksville, NY). The internal standard, 6β-hydroxytestosterone-d3, was purchased from Cerilliant (Round Rock, TX). The metabolite standards, 6β-, 2β-, and 2α-hydroxytestosterone, were purchased from Steraloids (Newport, RI). Therefore, we set out to examine the kinetics, regioselectivity, and stereoselectivity of testosterone oxidation in the CYP3A family and assess the suitability of the 2α-OH-T/6β-OH-T metabolite ratio as an endogenous biomarker for CYP3A7 activity. If this were to be the case, it could prove extremely useful for dosing calculations and pharmacokinetic modeling in infants, as there currently is no known endogenous biomarker for CYP3A7 and it is not ethical to dose infants with probe substrate cocktails to determine enzymatic activity (Strougo et al., 2014). +However, previous reports have indicated that CYP3A7 also produces 2α-hydroxytestosterone (2α-OH-T) and that a 2α-OH-T/6β-OH-T ratio may be a unique endogenous biomarker of the activity of the enzyme. The metabolism of testosterone to 6β-hydroxytestosterone (6β-OH-T) is a commonly used assay to evaluate human CYP3A enzyme activities. The testes are the source of more than 95% of the circulating testosterone in men, although the adrenal cortex produces large amounts of the testoster-one precursor steroids dehydroepiandrosterone (DHEA) and androstenedione. High blood titre of testosterone inhibits both pituitary gonadotrophs and hypothalamic releasing hormone by negative feedback mechanism (Fig. 6.11). Sometimes in liver testosterone is converted to 1 7-ketosteroids (Fig. 6.10). +
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