Anabolic Doping Agents

Deutsch, Daniel A. von; Abukhalaf, Imad K.; Lapu-Bula, Rigobert

doi:10.1007/978-1-61779-222-9_15

Cited by 4 publications

(2 citation statements)

References 96 publications

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“…There are several possible explanations for this discrepancy. The simplest is that, since finasteride was only administered at the point of decidualization stimulus, sufficient residual DHT was already present in the tissue to support a normal decidualization response ( 40 , 41 ). Although finasteride inhibits both type I and II 5α-reductase enzymes in rodents ( 24 , 25 ) some residual SRD5A1 activity will persist in the presence of finasteride ( 42 ) and this may also be sufficient to support decidualization.…”

Section: Discussionmentioning

confidence: 99%

A role for steroid 5 alpha-reductase 1 in vascular remodeling during endometrial decidualization

et al. 2022

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Decidualization is the hormone-dependent process of endometrial remodeling that is essential for fertility and reproductive health. It is characterized by dynamic changes in the endometrial stromal compartment including differentiation of fibroblasts, immune cell trafficking and vascular remodeling. Deficits in decidualization are implicated in disorders of pregnancy such as implantation failure, intra-uterine growth restriction, and pre-eclampsia. Androgens are key regulators of decidualization that promote optimal differentiation of stromal fibroblasts and activation of downstream signaling pathways required for endometrial remodeling. We have shown that androgen biosynthesis, via 5α-reductase-dependent production of dihydrotestosterone, is required for optimal decidualization of human stromal fibroblasts in vitro, but whether this is required for decidualization in vivo has not been tested. In the current study we used steroid 5α-reductase type 1 (SRD5A1) deficient mice (Srd5a1-/- mice) and a validated model of induced decidualization to investigate the role of SRD5A1 and intracrine androgen signaling in endometrial decidualization. We measured decidualization response (weight/proportion), transcriptomic changes, and morphological and functional parameters of vascular development. These investigations revealed a striking effect of 5α-reductase deficiency on the decidualization response. Furthermore, vessel permeability and transcriptional regulation of angiogenesis signaling pathways, particularly those that involved vascular endothelial growth factor (VEGF), were disrupted in the absence of 5α-reductase. In Srd5a1-/- mice, injection of dihydrotestosterone co-incident with decidualization restored decidualization responses, vessel permeability, and expression of angiogenesis genes to wild type levels. Androgen availability declines with age which may contribute to age-related risk of pregnancy disorders. These findings show that intracrine androgen signaling is required for optimal decidualization in vivo and confirm a major role for androgens in the development of the vasculature during decidualization through regulation of the VEGF pathway. These findings highlight new opportunities for improving age-related deficits in fertility and pregnancy health by targeting androgen-dependent signaling in the endometrium.

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Section: Discussionmentioning

confidence: 99%

A role for steroid 5 alpha-reductase 1 in vascular remodeling during endometrial decidualization

et al. 2022

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“…There are several possible explanations for this discrepancy. The simplest is that, since finasteride was only administered at the point of decidualisation stimulus, sufficient residual DHT was already present in the tissue to support a normal decidualisation response (Rittmaster et al, 1988, von Deutsch et al, 2012). Although finasteride inhibits both type I and II 5α-reductase enzymes in rodents (Livingstone et al, 2015, Thigpen and Russell, 1992) some residual SRD5A1 activity will persist in the presence of finasteride (Upreti et al, 2015) and this may also be sufficient to support decidualisation.…”

Section: Discussionmentioning

confidence: 99%

A Role for Steroid 5 alpha-reductase 1 in Vascular Remodelling During Endometrial Decidualisation

Shaw

Kirkwood

Rebourcet

et al. 2022

Preprint

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Decidualisation is the hormone-dependent process of endometrial remodelling that is essential for fertility and reproductive health. It is characterised by dynamic changes in the endometrial stromal compartment including differentiation of fibroblasts, immune cell trafficking and vascular remodelling. Deficits in decidualisation are implicated in disorders of pregnancy such as implantation failure, intra-uterine growth restriction, and pre-eclampsia. Androgens are key regulators of decidualisation that promote optimal differentiation of stromal fibroblasts and activation of downstream signalling pathways required for endometrial remodelling. We have shown that androgen biosynthesis, via 5α-reductase-dependent production of dihydrotestosterone, is required for optimal decidualisation of human stromal fibroblasts in vitro, but whether this is required for decidualisation in vivo has not been tested. In the current study we used steroid 5α-reductase type 1 (SRD5A1) deficient mice (Srd5a1-/- mice) and a validated model of induced decidualisation to investigate the role of SRD5A1 and intracrine androgen signalling in endometrial decidualisation. We measured decidualisation response (weight/proportion), transcriptomic changes, and morphological and functional parameters of vascular development. These investigations revealed a striking effect of 5α-reductase deficiency on the decidualisation response. Furthermore, vessel permeability and transcriptional regulation of angiogenesis signalling pathways, particularly those that involved vascular endothelial growth factor (VEGF), were disrupted in the absence of 5α-reductase. In Srd5a1-/- mice, injection of dihydrotestosterone co-incident with decidualisation restored decidualisation responses, vessel permeability, and expression of angiogenesis genes to wild type levels. Androgen availability declines with age which may contribute to age-related risk of pregnancy disorders. These findings show that intracrine androgen signalling is required for optimal decidualisation in vivo and confirm a major role for androgens in the development of the vasculature during decidualisation through regulation of the VEGF pathway. These findings highlight new opportunities for improving age-related deficits in fertility and pregnancy health by targeting androgen-dependent signalling in the endometrium.

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A review of the role of estrogen in dermal aging and facial attractiveness in women

Lephart

2018

J of Cosmetic Dermatology

121

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Estrogens are known to have protective and favorable influences on skin health; conversely, androgens oppose the actions of estrogens. Estrogen's chemical messages are transmitted via the classical nuclear hormone estrogen receptors (ER) alpha and beta and the rapid-acting G-coupled membrane estrogen receptor. Androgens [both testosterone and 5α-dihydrotestosterone (5α-DHT)] bind the same androgen receptor. Estrogen levels peak in the mid- to late 20s in women and then decline by 50% by 50 years of age and dramatically decrease further after menopause. The loss of estrogens with aging contributes to diminished dermal health, whereas estrogen hormone therapy [eg, oral conjugated equine estrogens (CEE)] restores skin health. Several reports suggest positive correlations between the levels of circulating estrogens and: (1) perceived age, (2) attractiveness, (3) enhanced skin health, and (4) facial coloration in women. Based upon a psychological dermato-endocrine perspective, the positive correspondence of high estrogens levels with perceived age and facial attractiveness in women especially with aging demonstrates the importance of hormonal influences on observed dermal health and youthful appearance.

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Anabolic Doping Agents

Cited by 4 publications

References 96 publications

A role for steroid 5 alpha-reductase 1 in vascular remodeling during endometrial decidualization

A role for steroid 5 alpha-reductase 1 in vascular remodeling during endometrial decidualization

A Role for Steroid 5 alpha-reductase 1 in Vascular Remodelling During Endometrial Decidualisation

A review of the role of estrogen in dermal aging and facial attractiveness in women

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