INSL3 produced by testes not replaced by TRT

[Robotics]

Any thoughts on this. Does hcg normalize INSL3 production?

A Single Hormone in Men May Predict Their Future Health

 

[madman]

Any thoughts on this. Does hcg normalize INSL3 production?

A Single Hormone in Men May Predict Their Future Health

Insulin-Like Factor 3 Serum Levels in 135 Normal Men and 85 Men with Testicular Disorders: Relationship to the Luteinizing Hormone-Testosterone Axis

Insulin-like factor 3 (INSL3) serum levels were measured in 135 andrologically well-characterized normal men and 85 patients with testicular disorders to i

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The Effects of Gonadotropin Suppression and Selective Replacement on Insulin-Like Factor 3 Secretion in Normal Adult Men

Abstract. Context: Gonadotropic regulation of the testicular Leydig cell hormone insulin-like factor 3 (INSL3) is incompletely characterized.Objective: The

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Serum insulin-like factor 3 is highly correlated with intratesticular testosterone in normal men with acute, experimental gonadotropin deficiency stimulated with low-dose human chorionic gonadotropin: a randomized, controlled trial

To study the potential role for using serum biomarkers, including insulin-like factor 3 (INSL3), 17α-hydroxyprogesterone, antimüllerian hormone, and i…

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DISCUSSION

In this placebo-controlled, randomized clinical trial we have shown that serum INSL3 concentrations in normal men decrease dramatically with acute gonadotropin suppression and increase in a dose–response relationship with low-dose hCG stimulation, correlating highly with IT-T and serum T concentrations. In contrast, serum INHB, AMH, and 17-OHP did not significantly change with acute gonadotropin suppression or hCG stimulation and did not correlate with IT-T. Our results expand upon previous observations by Bay et al. examining the effect of high-dose gonadotropin stimulation on INSL3 concentrations (19, 20). The prior data illustrate that INSL3 seems to be maximally produced at baseline in normal men and does not increase with gonadotropin stimulation (20). In infertile men with hypogonadotropic hypogonadism, high hCG doses are capable of stimulating otherwise suppressed INSL3 production (19). Here, the use of gonadotropin suppression with a GnRH antagonist, acyline, coupled with very-low-dose hCG stimulation (to mimic LH stimulation), demonstrates a dose–response relationship between hCG/LH stimulation and INSL3 concentrations in a low-gonadotropin environment.

Because serum INSL3 correlates highly with IT-T concentrations, serum INSL3 might be useful as a serum biomarker for the effect of hCG therapy and LH-like stimulation of Leydig cells. Studies evaluating INSL3 concentrations in hypogonadotropic hypogonadal men treated with hCG vs. T therapy have suggested that INSL3 production and secretion are regulated by LH rather than IT-T (20). Our data cannot help to distinguish whether LH or IT-T stimulates INSL3 production, because both correlate similarly with INSL3 in this study.




One limitation of this study is our limited sample size. Correlations of several of the hormones with one another approached but did not attain statistical significance in our study. Because the study was powered to determine the differences in intratesticular T between dose groups of hCG, it may have lacked the necessary power to identify all significant associations between the various hormones. Future, larger studies designed with adequate power to examine these relationships in men with infertility will be needed to clarify the relative utility of these serum markers for IT-T during hCG therapy. A second possible limitation is the use of normal men in this study, not infertile men. Future studies investigating the best serum biomarker for IT-T during hCG therapy should be conducted in infertile men, because the ability to extrapolate the findings discussed here may not reflect the associations observed in infertile men.




In summary, we demonstrated an acute decrease in serum INSL3 concentrations in response to gonadotropin suppression and a dose–response relationship between INSL3 and IT-T concentrations using low-dose hCG stimulation in normal men. We have also shown that serum INHB, AMH, and 17-OHP do not correlate significantly with IT-T. This work may have relevance in the use of serum INSL3 as a potential marker for IT-T concentrations. Although IT-T concentrations vary significantly among fertile men and reflect LH pulsatility.




TABLE 1 Baseline characteristics and baseline and posttreatment serum hormones of 31 participants by treatment group.

Box plot of serum INSL3 concentration in gonadotropin-suppressed subjects at baseline (n = 31) and on day 10 by treatment group (n =6 for the 0-IU hCG group, n = 7 for the 15-IU hCG group, and n =5 for the 60-IU hCG group and 125-IU hCG group). *P<.05 compared with baseline, 60-IU hCG group, and 125-IU hCG group. Dotted lines and gray shading represent the normal range for serum INSL3

(A–C) Correlations between posttreatment serum INSL3 for all 23 subjects receiving hCG therapy intratesticular T (A), serum T (B), and serum hCG (C). Dotted lines represent the lower limit of the normal range. Lines shown represent the best linear fit

 

[madman]

Male infertility and intratesticular T - insight into novel serum biomarkers

An update on male infertility and intratesticular testosterone— insight into novel serum biomarkers(2021) Karim Sidhom , Kapilan Panchendrabose , Uday Mann and Premal Patel Intratesticular testosterone is vital for spermatogenesis, male fertility, and virility. Currently, the only method to...

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INSULIN-LIKE FACTOR 3 (INSL3)

INSL3 is a peptide hormone synthesized in adult Leydig cells and has been previously shown to be able to act as a biomarker for Leydig cell functionality [45]. Additionally, since INSL3 is constitutively produced by adult Leydig cells, it is temporally reflective when Leydig cells have differentiated. INSL3 levels are therefore capable to represent the population of differentiated Leydig cells and are more of an accurate predictor than serum testosterone. Serum testosterone is regulated by the HPG axis and undergoes large diurnal fluctuations [45, 46]. The large variability throughout the day and between patients with the same diseases makes it less of a candidate to represent Leydig cell function. INSL3 has also been shown to likely be solely produced from Leydig cells and its regulation is unaffected by LH. Bay et al. assessed the levels of serum INSL3 in 135 healthy males and 21 anorchid men using time-resolved fluorescence immunoassays and found median INSL3 levels were 0.99 ng/ml and 0.05 ng/ml respectively [47]. They also found INSL3 levels to be 15 times higher in blood samples drawn from vena spermatic compared to peripheral blood of two infertile males. This is suggestive that INSL3 may be solely localized in the testes.

INSL3 can be an insightful biomarker for patients undergoing hCG monotherapy. Although INSL3 levels have been observed to not significantly differ in hypogonadal patients within 72 and 96 h, hCG was highly associated with higher levels of INSL3. Hence, it is thought that hCG acts to differentiate Leydig cells in hypogonadal men. The Roth et al. study previously mentioned further corroborates the effects of hCG by administering dose-dependent injections subcutaneously consisting of gonadotropin-releasing hormone antagonist, acyline, and hCG or testosterone gel for 10 days in healthy males. Patients receiving only the antagonist had significantly lower INSL3 levels than the baseline and higher doses of hCG normalized INSL3 again [48]. These levels are directly correlated with serum testosterone levels.