Extremely high inhibin B - possible new clue

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#1

Perhaps a new clue especially for those with ejaculatory disorders and/or low FSH/poor response of FSH to clomiphene (I have all of these). Inhibin B is a measure of Sertoli cell amount in the testis, and/or activity of such cells.

Went off all medications and supplements for a few weeks to clear out my system for a new round of bloodwork. As expected T dropped in half from “on clomiphene” status.

The most startling result was my inhibin B level. It was over 3x normal.
Various resources indicate normal inhibin B levels of between 140 and 180 ng/dL. Infertile men are typically around 80 pg/mL. Quest’s “normal range” per their EndoManual is < 305 pg/mL.

en.wikipedia.org/wiki/Activin_and_inhibin
see Clinical Significance section.

en.wikipedia.org/wiki/Activin_and_inhibin

Mine is over 3x normal levels. Only possible reason for this high a level that I have found is lead poisoning - in studies of older lead smelter workers inhibin B of over 300 was commonly found.

ncbi.nlm.nih.gov/pubmed/15910540

So I had a 24 hour urine test for lead (provocative using a chelating agent). Was honestly hoping I had lead poisoning as at least that is curable. No luck, lead and other toxic metals were below the detectability range.

This thread is for discussion of inhibin B levels. I would recommend anyone with either abnormally low FSH (< 3 IU/L, secondary hypogonadism) or abnormally high FSH get it tested. Will talk to Mew about adding a Sticky to track Inhibin B, with a new link to be added below:

#2

Interesting Kazman. Wiki states:

Since we are androgen deprived I would expect our Inhibin to be low, not high. The fact that it is high would explain why our FSH is low, which would lead to low T. Seems like this would point to a possible problem with Sertoli cells. What did your endo have to say about your reading?

#3

My endo was, I think, expecting inhibin to be low. He added the test after I complained about ejaculatory disorders/anorgasmia. He did not know what to make of the very high inhinin B, I had to show him the Toxicology book and abstracts I had found regarding lead poisoning.

This sort of fits - high inhibin levels suppress gonadotropin secretion which would explain the secondary hypogonadism.

There are a couple of abstracts out there pointing to inhibin secreting granulomas in women’s ovaries, but nothing on men.

I am having inhibin restested soon, this time on clomiphene citrate (lower dose than previously).

#4

Kazman what do you think about this study?
[Size=4]Androgens rapidly increase the cytosolic calcium concentration in Sertoli cells.[/size]
Gorczynska E, Handelsman DJ.

Department of Obstetrics and Gynecology, University of Sydney, New South Wales, Australia.

Abstract
We demonstrate that androgens rapidly and specifically increase intracellular calcium in Sertoli cells, investigate the mechanism, and suggest the unifying hypothesis that calcium might be a common intracellular molecular effector to explain the known synergism between FSH and testosterone (T) action on Sertoli cells in support of spermatogenesis. In freshly isolated Sertoli cells, T and its 5 alpha-reduced metabolite dihydrotestosterone increased intracellular calcium from 83 +/- 4 to 147 +/- 8 and 167 +/- 29 nM, respectively, whereas estradiol had minor (117 +/- 9 nM) and progesterone no (80 +/- 6 nM) effect. The effect of T was rapid (20-40 sec) and inhibited by 1) preincubation with either a pure nonsteroidal antiandrogen (hydroxyflutamide) or a 5 alpha-reductase inhibitor (finasteride) or 2) removal of extracellular calcium (47 +/- 4 nM) or pharmacological blockade of voltage-activated (62 +/- 5 nM) or voltage-independent (55 +/- 14 nM) membrane calcium channels. These findings suggest that the T-induced rise in Sertoli cell cytosolic calcium involves sequential 5 alpha-reduction, binding to a classical androgen receptor, and activation of transmembrane influx of extracellular calcium. Immobilization of T by conjugation to a large carrier molecule (BSA) to prevent steroid entry into Sertoli cells also resulted in a rapid increase in cytosolic calcium to a similar magnitude as unconjugated T, consistent with a plasma membrane site of action. This finding together with the rapid cytosolic calcium rise caused by T argues for the possible existence of a short term, nongenomic effects in hormonal regulation of Sertoli cell function in addition to the well known, slower genomic response.

ncbi.nlm.nih.gov/pubmed/7720654

#5

tim perhaps I’m not quite grasping the connection this article has with the discussion in this thread - it does show that finasteride effects Seritoli cells, and it appears from the prior cited reference that inhibin is created in the Sertoli cells, but beyond this the connection isn’t jumping out at me.

Anyone with low FSH and/or sluggish response of FSH to clomiphene stimulation please get inhibin B tested.

#6

I just visited my Dr.yesterday and requested him to write test for my inhibin and Activin, He kicked me out. It is frustrating if you slap some one Police will arrest you and put you in jail but people who destroyed our lives are on the loose. I am to the point where I can do anything. If my life has destroyed these bast… so called herbalists who are writing books to mislead people, people who are living on our taxes in health department and allowing poison to be sold OTC, have no right to enjoy their lives.

#7

Activin and inhibin have opposite effects on steroid 5 alpha-reductase activity in genital skin fibroblasts.

Abstract

The transforming growth factor beta (TGF-beta) superfamily includes several closely related peptides including the activins and inhibins. Since we recently reported that TGF-beta 1 and beta 2 are potent inducers of steroid 5 alpha-reductase (5 alpha R), we have now studied the effects of these other peptides using primary cultures of human scrotal skin fibroblasts. Recombinant human activin A or inhibin A were added to cultured cells (2 x 10(5) cells) for 2 days in a serum free media and 5 alpha R activity was measured by the %-conversion of tracer 3H-testosterone to dihydrotestosterone (DHT) over a 4-h period. Activin significantly stimulated 5 alpha R activity in a dose related manner (control 3.0 0.4%, activin (1.2 x 10(-9) M) 6 0.7%, P < 0.01, (2.4 x 10(-9) M) 8.5 0.6%, P < 0.001). In comparison, androgen (DHT 10(-7) M) induction of 5 alpha R was 4.7 0.2%, P < 0.05. Combined exposure of fibroblasts to activin (1.2 x 10(-9) M) and androgen (10(-7) M) did not result in additive or synergistic effect on 5 alpha R activity. In contrast, exposure of cells to an androgen (10(-7) M) and TGF-beta (2 x 10(-10) M) led to synergistic effects on 5 alpha R activity (control 1.5 0.1%, DHT 2.6 0.2% TGF-beta 1 4.8 0.5, TGF-beta 1 + DHT 9.2 1.2%)…

In contrast inhibin inhibits androgen induction of 5aR. Activin and inhibin, two closely related molecules, potentially play oppisite roles in dht formation in sexual tissue.

sciencedirect.com/science/article/pii/0303720794034302

Sorry Kazman, couldnt cut and paste properly. Have a read.

What do you think?