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Long-Term Effects of Perinatal Treatment with Sex Steroids and Related Substances on Reproductive Organs of Female Mice
Published in Takao Mori, Hiroshi Nagasawa, Toxicity of Hormones in Perinatal Life, 2020
John-Gunnar Forsberg, Taisen Iguchi
In mice, the effects of androgens, testosterone, and testosterone propionate appear to be similar in effect to estradiol-17β.44-48 Treatment with 5α-dihydrotestosterone, a nonaromatizable androgen, has been shown to be effective in this respect49,50 and 5β-dihydrotestosterone which is biologically inactive on adult reproductive organs also induces persistent vaginal cornification.51 After transplantation into syngeneic ovariectomized hosts, a majority of neonatal mouse vaginas cultured in a medium containing either estrogens or 5α-dihydro-testosterone exhibited estrogen-independent proliferation and cornification of the epithelium, whereas only 15% of neonatal vaginas transplanted after prior exposure to testosterone in vitro showed a proliferation of the epithelium.52 These findings suggest that estrogens and nonaromatizable androgens are able to act directly on the vaginal epithelium of newborn mice to cause some permanent changes, while aromatizable androgens such as testosterone act on the epithelium after conversion into estradiol or some related estrogens. Recent studies have demonstrated that aromatase and/or 5α-reductase inhibitors can slightly decrease the incidence of the vaginal changes induced by testosterone.138 At present, it is not known whether or not different mechanisms are involved in the induction of the irreversible vaginal changes caused by different hormones. Androgen treatment often produces a persistent mucification of the vaginal epithelium associated with irreversible proliferation (Figure 6). In addition, direct administration of testosterone propionate to fetuses is especially effective in the production of vaginal changes.53
Sex differences in COPD management
Published in Expert Review of Clinical Pharmacology, 2021
Maria Gabriella Matera, Josuel Ora, Luigino Calzetta, Paola Rogliani, Mario Cazzola
Nevertheless, it is still unclear whether sex hormones might modify β2-adrenoceptor (AR) mediated bronchodilation. It was shown that testosterone potentiated the relaxation induced by isoprenaline in pig bronchus via a nongenomic effect that involved the inhibition of catechol-O-methyl transferase (COMT) or abolition of extraneuronal uptake [68]. It was also found that 5α-dihydrotestosterone, which is a reduced metabolite of testosterone, potentiated the relaxation induced by salbutamol in the bovine tracheal airway smooth muscle [69]. However, in another study, 5α-dihydrotestosterone, and also 5β-dihydrotestosterone and estradiol, did not significantly modify long-term relaxation of isolated preparations of bovine trachea induced by salbutamol, whereas testosterone facilitated the acute response to salbutamol, delayed the beginning of the loss of the long-term spasmolytic effect of salbutamol and decreased the percentage of reversion to salbutamol [70]. Furthermore, in guinea pig, chronic airway smooth muscle exposure to testosterone augmented the expression of β2-ARs and evoked an increase in the relaxing responses to salbutamol [71]. All these findings suggest that androgens might modulate the airway smooth muscle tone, facilitating relaxation via β2-ARs [72].
Steroid hormones and pregnancy
Published in Gynecological Endocrinology, 2019
Nancy Noyola-Martínez, Ali Halhali, David Barrera
Indeed, it has been demonstrated that T is transported to fetal liver to produce 5β-reduced androgens such as 5β-dihydrotestosterone (5β-DHT) due to the action of 5β-reductase. Meanwhile, 5α-reduced metabolites such as 5α-DHT, androsterone and epienadrosterone are produced in fetal lung and gastrointestinal tract [12]. These findings showed the conversion of the dihydro and tetrahydro derivatives in the fetal compartment. Besides, in the fetal liver DHEAS may contribute to the formation of 16α-DHEAS or it can be hydroxylated on carbon 7 of the molecule for the production of 7α and 7β derivatives. In addition, T can be biotransformed into E2 which in turn is converted to estretol (E4) by 15α-hydroxylase in the fetal liver [13,14]. However, the biological significance of these steroids in many cases remains elusive.
Vasoactive androgens: Vasorelaxing effects and their potential regulation of blood pressure
Published in Endocrine Research, 2018
Lucía Isidoro, Mercedes Ferrer, Mercedes Perusquía
Of particular interest is that these are structurally specific effects of the androgen molecule due to the fact that their potency and efficacy to provoke those effects is different for each androgen, thus we have identified that the 5β-reduced metabolite of TES, 5β-dihydrotestosterone (5β-DHT), is the most potent androgen to induce: (i) vasorelaxation 1,3,11–14; and (ii) reduction on systemic BP 9,10 while its epimer, 5α-dihydrotestosterone (5α-DHT), is less effective, and even less effective than TES, the precursor of both 5α- and 5β-DHT.