(27-03-2015, 12:28 PM)-Clelia- Wrote: What i do not understand up there underlined is:
why addiction of DHT didn't decrease gland morphology in adult mammary gland?
why affected just the midpuberty, retarding development?
maybe in the adult mammary gland, DHT in extra amount, is it converted in 3-diol? so it can neutralize is own androgenic effect? I don't know...maybe it's that back-door effect, but result is not estrogenic, otherwise mammary gland should have developed..
I could understand just flutamide action... in midpuberty should work less because of less presence of AR receptor. When AR receptors increase in post-puberty, the antagonism of them promote growing.
If we low DHT, we should mimic a bit flutamide action. And also, more testosterone will be converted in estradiol, as mentioned in your sign
Hi Clelia,
Hope you had a good weekend,
Sorry I jumped ahead a few spots,
getting back to your question. 3b-diol does explain the back door response. I'm just wondering if there's a re-absorption response before being excreted?, (e.g. re-activate DHT, one more time) as seen with estrogen metabolites. I dunno?,
But in males it does seem that 3-diol has estrogen action (ER-b) in epithelia of efferent ductules and the epididymis. I'm going to post about 4-5 posts regarding this process (male ER-b) that I posted a few months ago if that's ok.
If rather focus on mammary DHT's fine too, either way, there's much to solve with your help.
(29-12-2014, 07:15 PM)Lotus Wrote: So what if there was way to influence an estrogen action in the Leydig cells since they already include estrogen receptors. Well, a pathway needs to be established. Here is one possible source, or could be a possible action.
Sperm, a source of estrogen
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1518866/
Environ Health Perspect. Oct 1995; 103(Suppl 7): 59–62.
PMCID: PMC1518866
Research Article
Sperm, a source of estrogen.
Other info: it's being researched already.
Estrogen signaling in testicular cells.
Aromatase transforms irreversibly androgens into estrogens and is present in the endoplasmic reticulum of various tissues including the mammalian testis. In rat all testicular cells except peritubular cells express aromatase. Indeed in adult rat germ cells (pachytene spermatocytes and round spermatids) we have demonstrated the presence of a functional aromatase (transcript, protein and biological activity) and the estrogen output is equivalent to that of Leydig cells. In addition in the adult rat, transcripts of aromatase vary according to the germ cell type and to the stages of seminiferous epithelium. By contrast with the androgen receptors mainly localized in somatic cells, estrogen receptors (ERs) are described in most of the testicular cells including germ cells. Moreover, besides the presence of high affinity ERα and/or ERβ, a rapid membrane effect has been recently reported and we demonstrated that GPR30 (a transmembrane intracellular estrogen receptor) is expressed in adult rat pachytene spermatocytes. Therefore estrogens through both GPR30 and ERα are able to activate the rapid EGFR/ERK/c-jun signaling cascade, which in turn triggers an apoptotic mitochondrial pathway involving an increase in Bax expression and a concomitant reduction of cyclin A1 and B1 gene levels. In another study in round spermatids of adult rat we have shown that the rapid membrane effect of estradiol is also efficient in controlling apoptosis and maturation / differentiation of these haploid germ cells. In man the presence of a biologically active aromatase and of estrogen receptors has been reported in Leydig cells, but also in immature germ cells and ejaculated spermatozoa. Thus the role of estrogen (intracrine, autocrine and / or paracrine) in spermatogenesis (proliferation, apoptosis, survival and maturation) and more generally, in male reproduction is now evidenced taking into account the simultaneous presence of a biologically active aromatase and the widespread distribution of estrogen receptors especially in haploid germ cells.
(29-12-2014, 08:35 PM)Lotus Wrote: (29-12-2014, 08:29 PM)elainecd Wrote: oK then I just have to ask...
Would men's sperm be a significant source of aromatase?
I think so, the study concluded that Leydig cells, germ cells, and seminiferous tubules all showed positive stains for aromatase. But it has to do more with the head (tip) of sperm.
I take that back, it's the tail that has the most aromatase and the head of the epididymis displays estrogen receptors where estrogen synthesis occurs.
Summary diagram of potential estrogen action in epithelia of efferent ductules and the epididymis. At least 4 potential pathways are considered. 1) testosterone (T) can enter the cell or be converted to E2 by aromatase (Arom) found in luminal sperm [54]. Testosterone binds AR and translocates into the nucleus, where it binds to AREs, on the promoter regions of genes with or without EREs. 2) E2 will either enter the cell, as did testosterone or bind the membrane ESR (mESR1). It remains controversial whether E2 binds GPR30 in the membrane [144] or collaborates with mESR1 to mediate epidermal growth factor receptor (EGFR) activation (nonclassical) of kinases and phosphorylation [180]. It is well known that E2 binds ESR1 and translocates into the nucleus for classical mediation of transcription through EREs and recruitment of numerous cofactor proteins (C1–3). It is unknown how AR and ESR1 compete for these cofactors, or what happens when the steroid balance is altered in a cell expressing both receptors. 3) The ESR1 can also be activated through phosphorylation and mediate transcription through the ERE. 4) It is well documented in other tissues that mESR1 binds E2, resulting in very rapid cell signaling [84, 175, 178]. This rapid steroid activity through the membrane receptor involves caveolin-1, G proteins, and the phosphorylation/dephosphorylation cascades, which mediate transcription either through the ESR1/ERE or other transcription factors (TF).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071263/
I think we made an important step in solving the Estrogen action in Genetic Males and NBE.
Or a 67 yard field goal.