Testosterone and the Androgen Receptor

Gerald, Thomas; Raj, Ganesh V.

doi:10.1016/j.ucl.2022.07.004

Cited by 16 publications

(10 citation statements)

References 61 publications

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“…The production of TT is regulated by the hypothalamic-pituitary axis under the direction of gonadotropin-releasing hormone and LH. DHT is converted by TT under the catalysis of 5-a reductase [ 68 ]. Apart from maintaining normal male sexual characteristics, androgens exert biological functions, including regulating cell metabolism, neuronal proliferation, and neuronal excitability [ 69 ].…”

Section: The Influence Of Androgen On Opioid-induced Analgesiamentioning

confidence: 99%

The role of gonadal hormones in regulating opioid antinociception

Xu,

Jin,

Wang

et al. 2024

Annals of Medicine

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Opioids are the most prescribed drugs for the alleviation of pain. Both clinical and preclinical studies have reported strong evidence for sex-related divergence regarding opioid analgesia. There is an increasing amount of evidence indicating that gonadal hormones regulate the analgesic efficacy of opioids. This review presents an overview of the importance of gonadal steroids in modulating opioid analgesic responsiveness and focuses on elaborating what is currently known regarding the underlyingmechanism. We sought to identify the link between gonadal hormones and the effect of oipiod antinociception.

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Section: The Influence Of Androgen On Opioid-induced Analgesiamentioning

confidence: 99%

The role of gonadal hormones in regulating opioid antinociception

Xu,

Jin,

Wang

et al. 2024

Annals of Medicine

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“…Gonadotropin-releasing hormone from the hypothalamus induces production of LH from the anterior pituitary. Leydig cells present in the testicular interstitial tissue in males produce LH receptors enabling circulating LH to induce testosterone steroidogenesis as well as Leydig cell growth and proliferation (Gerald & Raj, 2022).…”

Section: Me Tabolis M-g Ener Almentioning

confidence: 99%

“…Gonadotropin‐releasing hormone from the hypothalamus induces production of LH from the anterior pituitary. Leydig cells present in the testicular interstitial tissue in males produce LH receptors enabling circulating LH to induce testosterone steroidogenesis as well as Leydig cell growth and proliferation (Gerald & Raj, 2022). Steroidogenesis occurs along the pathways described in Figure 3 and relies on cholesterol as a biosynthetic precursor transported into the cell by lipoprotein receptors, then pregnenolone formation in Leydig cell mitochondria, followed by a battery of intracellular enzymes comprising cytochrome P450 oxidases and hydroxysteroid dehydrogenase.…”

Section: Metabolism—generalmentioning

confidence: 99%

“…As androgens bound to SHBG are generally unavailable for bioactivity, alterations in SHBG levels have significant effects on androgen effects. Estrogens, antiestrogens, antiepileptic drugs, age, and hyperthyroidism can increase SHBG levels, whereas exogenous androgens, glucocorticoids, growth hormone therapy, hypothyroidism, obesity, and hyperinsulinemia may decrease SHBG (Gerald & Raj, 2022). Testosterone is also the precursor to hormones with potent peripheral activity, namely dihydrotestosterone formed primarily in the skin, liver, and the genitourinary tract by 5α‐reductase, and estradiol formed by Cyp19 with important effects on bone mineralization, epiphyseal plate closure, and insulin sensitivity (Rodd et al, 2004; Simpson et al, 2002; Swerdloff et al, 2017; Yokota‐Nakagi et al, 2022).…”

Section: Metabolism—generalmentioning

confidence: 99%

“…Enzyme abbreviations include (1) Cyp11A1, that is, cytochrome P450 11A1, comprising cholesterol side‐chain cleavage activity; (2) Cyp17, cytochrome P450 17A1 including 17‐alpha‐hydroxylase and 17,20‐lyase activities; (3) Cyp19, cytochrome P450 aromatase activity; (4) 3β‐HSDII, 3β‐hydroxysteroid dehydrogenase, comprising 3‐keto conversion from 3‐hydroxy groups as well as delta 5–4 isomerase activity; (5) 17β‐HSD3, 17β‐hydroxysteroid dehydrogenase; and (6) 5α‐reductase, comprising activity for 3‐oxo‐5α‐steroid interconversion with 3‐oxo‐Δ 4 ‐steroid. Adapted from Gerald and Raj (2022) and Sato et al (2016).…”

Section: Metabolism—generalmentioning

confidence: 99%

See 2 more Smart Citations

A review of current chemistry, pharmacology, and regulation of endogenous anabolic steroids testosterone, boldenone, and nandrolone in horses

Dirikolu

Lehner

2023

Vet Pharm & Therapeutics

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Anabolic androgenic steroids are synthetic substances related to the male sex hormones (androgens). These agents promote the growth of skeletal muscle (anabolic effects) and the development of male sexual characteristics (androgenic effects). Anabolic steroids have been illegally used for many years as performance‐enhancing drugs in human, equine, and canine sports and as growth promoters in livestock reared to provide meat for human consumption. The analytical challenge to developing effective means of control within these fields has been exacerbated by the reported endogenous nature of some of these steroids. Anabolic steroids have been employed extensively in equine practice over the past 50 years. Their usefulness is largely dependent on subjective opinions, as only minimal studies investigating pharmacodynamics have been carried out in horses. Therefore, their use will vary markedly between practitioners depending on their personal experiences and pressures by trainers to use them. They form part of rational therapy in a variety of conditions. In addition to their use for increasing muscle mass, they are used to varying extents in the raising of yearlings and in the training and racing of horses with the view of improving performance. The use of these agents is prohibited in the horseracing industry by the Association of Racing Commissioners International (ARCI), International Federation of Horseracing Authorities (IFHA), and Fédération Equestre Internationale (FEI).

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AOP Report: An Upstream Network for Reduced Androgen Signaling Leading to Altered Gene Expression of Androgen Receptor–Responsive Genes in Target Tissues

Draskau,

Rosenmai,

Bouftas

et al. 2024

Enviro Toxic and Chemistry

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Adverse outcome pathways (AOPs) can aid with chemical risk assessment by providing plausible links between chemical activity at the molecular level and effect outcomes in intact organisms. Because AOPs can be used to infer causality between upstream and downstream events in toxicological pathways, the AOP framework can also facilitate increased uptake of alternative methods and new approach methodologies to help inform hazard identification. However, a prevailing challenge is the limited number of fully developed and endorsed AOPs, primarily due to the substantial amount of work required by AOP developers and reviewers. Consequently, a more pragmatic approach to AOP development has been proposed where smaller units of knowledge are developed and reviewed independent of full AOPs. In this context, we have developed an upstream network comprising key events (KEs) and KE relationships related to decreased androgen signaling, converging at a nodal KE that can branch out to numerous adverse outcomes (AOs) relevant to androgen‐sensitive toxicological pathways. Androgen signaling represents an extensively studied pathway for endocrine disruption. It is linked to numerous disease outcomes and can be affected by many different endocrine‐disrupting chemicals. Still, pathways related to disrupted androgen signaling remain underrepresented in the AOP‐wiki, and endorsed AOPs are lacking. Given the pivotal role of androgen signaling in development and function across vertebrate taxa and life stages of both sexes, this upstream AOP network serves as a foundational element for developing numerous AOPs. By connecting the upstream network with various downstream AOs, encompassing different species, it can also facilitate cross‐species extrapolations for hazard and risk assessment of chemicals. Environ Toxicol Chem 2024;00:1–9. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

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Testosterone and the Androgen Receptor

Cited by 16 publications

References 61 publications

The role of gonadal hormones in regulating opioid antinociception

The role of gonadal hormones in regulating opioid antinociception

A review of current chemistry, pharmacology, and regulation of endogenous anabolic steroids testosterone, boldenone, and nandrolone in horses

AOP Report: An Upstream Network for Reduced Androgen Signaling Leading to Altered Gene Expression of Androgen Receptor–Responsive Genes in Target Tissues

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