The The 56 kDa androgen binding protein is an aldehyde dehydrogenase (RALDH1)

General Discussion
#1

This is retinoic acid signaling and synthesis.

Aldehyde dehydrogenase 1 family, member A1 , also known as ALDH1A1 or retinaldehyde dehydrogenase 1 (RALDH1)

RALDH1 (ALDH1A1) was the first member of the ALDH family found to possess in vitro activity for oxidation of retinal- dehyde to RA (18, 20). … Our results indicate that RALDH1 plays a role in oxidation of retinaldehyde to RA for clearance of excess retinol in adult mice, thus acting downstream of ADH1


We have described a 56 kDa protein from genital skin fibroblasts that specifically binds androgen and that is generally not expressed in genital skin fibroblasts from patients with androgen insensitivity due to genetic defects of the androgen receptor. We have isolated a partial cDNA clone for the 56 kDa protein from an expression library of genital skin fibroblasts. In vitro translation of message selected with this clone faithfully produces the 56 kDa protein which can be immunoprecipitated with an anti-56 kDa antiserum. Northern blots probed with this clone show a 2.2 kb message, which parallels the expression of the 56 kDa protein. The sequence of this 998bp clone is identical to human liver aldehyde dehydrogenase 1, the cytoplasmic isoenzyme. On activity gels of genital skin fibroblast cytosol covalently labelled with androgen, aldehyde dehydrogenase activity comigrates with the single band labelled specifically with androgen. Thus, the 56 kDa androgen binding protein is an aldehyde dehydrogenase, which is prominently expressed in normal genital skin fibroblasts, but not in non-genital skin fibroblasts.

You see how closely these two could work together.

Sex specific retinoic acid signaling is required for the initiation of urogenital sinus bud development


These data identify RA as a major player in the initiation of prostate development, together with androgens.

We show that sex specific retinoic acid is required for male UGS bud initiation.
An increase in retinoic acid can lead to prostate-like formation in females.

#2

More on this.

# Raldh1 promotes adiposity during adolescence independently of retinal signaling

Raldh1 has multiple functions, however. It serves as an androgen binding-protein [37–39], and functions in the cornea and lens of mammalian eyes as eta-crystallin [40]. Raldh1 recognizes multiple substrates, including oxazaphosphoranes [41] and aldehyde lipid peroxidation products, such as malondialdehyde and nonenal [42]. Raldh1 also contributes to γ-aminobutyric acid biosynthesis in dopaminergic neurons [43]. Unlike other Raldh, Raldh1 localizes to both cytosol, where conversion of retinal into RA occurs, and in the nucleus, not known to biosynthesize RA [5]. Hence, Raldh1 has multiple functions independent of retinoid metabolism.

An androgenic affinity ligand covalently binds to cytosolic aldehyde dehydrogenase from human genital skin fibroblasts

A 56 kDa protein expressed in human genital skin fibroblasts was first identified by independent laboratories on the basis of its specific expression in androgen target cells and its ability to covalently bind androgenic affinity ligands. Recently, immunoscreening of a cDNA library with antisera directed against this protein resulted in the isolation of a partial cDNA clone identical to human cytosolic aldehyde dehydrogenase (ALDH1). We report here the preparation of a full-length cDNA encoding ALDH1 from human genital fibroblasts. Translation of the encoded protein in a cell-free system yields a 56 kDa product that can be covalently radiolabeled with [3H]dihydrotestosterone 17 beta-bromoacetate (DHT-BA). Expression of the full-length clone in mammalian cells also results in expression of a 56 kDa DHT-BA binding protein. The covalent binding of DHT-BA by ALDH1 is an intrinsic property of the enzyme and is not dependent on androgen receptor expression.

BIOLOGICAL ROLE OF HUMAN CYTOSOLIC ALDEHYDE
DEHYGROGENASE 1: HORMONAL RESPONSE, RETINAL
OXIDATION AND IMPLICATION IN TESTICULAR FEMINIZATION
This paper describes the retinal oxidation activity of the human ALDH1, the existence of glucocorticoid response elements in the ALDH1 gene and the biological role of ALDH1, including
the pathogenesis of the X-linked, androgen receptor-negative
testicular feminization.

^Meaning testicular feminization not related to the androgen receptor.

#3

I hope for a cure

1 Like
#4

Again the question would be could retinoic acid be the missing link?
Not androgens.
When you go down the line of all the symptoms people are experiencing, I think this might fit better.

Enzymes involved in retinoic acid synthesis are expressed in the UGS mesenchyme in a sex specific manner and addition of ligand to female tissue is able to induce prostate-like bud formation in the absence of androgens, albeit at reduced potency.

2 Likes
#5

This gives me hope.

#6

I think in relation to raldh1 creating adiposity and RA seems a little strange, RA doesn’t seem to increase obesity according to some studies.

Regarding RA not androgens as the link, did it feel like a boost in Androgens when you experimented with vitamin A?