PMID- 31981690
OWN - NLM
STAT- MEDLINE
DCOM- 20200804
LR  - 20200804
IS  - 1095-6840 (Electronic)
IS  - 0016-6480 (Linking)
VI  - 290
DP  - 2020 May 1
TI  - Consequences of steroid-5alpha-reductase deficiency and inhibition in vertebrates.
PG  - 113400
LID - S0016-6480(19)30507-6 [pii]
LID - 10.1016/j.ygcen.2020.113400 [doi]
AB  - In 1974, a lack of 5alpha-dihydrotestosterone (5alpha-DHT), the most potent androgen 
      across species except for fish, was shown to be the origin of a type of 
      pseudohermaphrodism in which boys have female-like external genitalia. This human 
      intersex condition is linked to a mutation in the steroid-5alpha-reductase type 2 
      (SRD5alpha2) gene, which usually produces an important enzyme capable of reducing the 
      Delta(4)-ene of steroid C-19 and C-21 into a 5alpha-stereoisomer. Seeing the potential of 
      SRD5alpha2 as a target for androgen synthesis, pharmaceutical companies developed 
      5alpha-reductase inhibitors (5ARIs), such as finasteride (FIN) and dutasteride (DUT) 
      to target SRD5alpha2 in benign prostatic hyperplasia and androgenic alopecia. In 
      addition to human treatment, the development of 5ARIs also enabled further 
      research of SRD5alpha functions. Therefore, this review details the morphological, 
      physiological, and molecular effects of the lack of SRD5alpha activity induced by 
      both SRD5alpha mutations and inhibitor exposures across species. More specifically, 
      data highlights 1) the role of 5alpha-DHT in the development of male secondary sexual 
      organs in vertebrates and sex determination in non-mammalian vertebrates, 2) the 
      role of SRD5alpha1 in the synthesis of the neurosteroid allopregnanolone (ALLO) and 
      5alpha-androstane-3alpha,17beta-diol (3alpha-diol), which are involved in anxiety and sexual 
      behavior, respectively, and 3) the role of SRD5alpha3 in N-glycosylation. This review 
      also features the lesser known functions of SRD5alphas in steroid degradation in the 
      uterus during pregnancy and glucocorticoid clearance in the liver. Additionally, 
      the review describes the regulation of SRD5alphas by the receptors of androgens, 
      progesterone, estrogen, and thyroid hormones, as well as their differential DNA 
      methylation. Factors known to be involved in their differential methylation are 
      age, inflammation, and mental stimulation. Overall, this review helps shed light 
      on the various essential functions of SRD5alphas across species.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Robitaille, Julie
AU  - Robitaille J
AD  - Centre Eau Terre Environnement, Institut national de la recherche scientifique 
      (INRS), Quebec City, QC, Canada.
FAU - Langlois, Valerie S
AU  - Langlois VS
AD  - Centre Eau Terre Environnement, Institut national de la recherche scientifique 
      (INRS), Quebec City, QC, Canada. Electronic address: valerie.langlois@inrs.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200122
PL  - United States
TA  - Gen Comp Endocrinol
JT  - General and comparative endocrinology
JID - 0370735
RN  - EC 1.3.99.5 (3-Oxo-5-alpha-Steroid 4-Dehydrogenase)
RN  - EC 1.3.99.5 (steroid-5alpha-reductase type 2)
SB  - IM
MH  - 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/*deficiency
MH  - Animals
MH  - Female
MH  - Male
MH  - Vertebrates/*genetics
OTO - NOTNLM
OT  - 5alpha-reductase inhibitors
OT  - Allopregnanolone
OT  - Dihydrotestosterone
OT  - N-glycosylation
OT  - Steroid-5alpha-reductase
EDAT- 2020/01/26 06:00
MHDA- 2020/08/05 06:00
CRDT- 2020/01/26 06:00
PHST- 2019/10/15 00:00 [received]
PHST- 2020/01/13 00:00 [revised]
PHST- 2020/01/20 00:00 [accepted]
PHST- 2020/01/26 06:00 [pubmed]
PHST- 2020/08/05 06:00 [medline]
PHST- 2020/01/26 06:00 [entrez]
AID - S0016-6480(19)30507-6 [pii]
AID - 10.1016/j.ygcen.2020.113400 [doi]
PST - ppublish
SO  - Gen Comp Endocrinol. 2020 May 1;290:113400. doi: 10.1016/j.ygcen.2020.113400. 
      Epub 2020 Jan 22.