Steroid hormone binding sites

Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, , p = × 10(-106)), PRMT6 (rs17496332, , p = × 10(-11)), GCKR (rs780093, , p = × 10(-16)), ZBTB10 (rs440837, , p = × 10(-09)), JMJD1C (rs7910927, , p = × 10(-35)), SLCO1B1 (rs4149056, , p = × 10(-08)), NR2F2 (rs8023580, , p = × 10(-12)), ZNF652 (rs2411984, , p = × 10(-14)), TDGF3 (rs1573036, , p = × 10(-14)), LHCGR (rs10454142, , p = × 10(-07)), BAIAP2L1 (rs3779195, , p = × 10(-08)), and UGT2B15 (rs293428, , p = × 10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci -UGT2B15 was significant in men only (men p = × 10(-08), women p = , heterogeneity p = ). Additionally, three loci showed strong sex-differentiated effects: -SHBG and -TDGF3 were stronger in men, whereas -ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ~% and ~% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.

As demonstrated in progesterone receptor-deficient mice, the physiological effects of progesterone depend completely on the presence of the human progesterone receptor (hPR), a member of the steroid-receptor superfamily of nuclear receptors. The single-copy human (hPR) gene uses separate promoters and translational start sites to produce two isoforms, hPR-A and -B, which are identical except for an additional 165 amino acids present only in the N terminus of hPR-B. [12] Although hPR-B shares many important structural domains with hPR-A, they are in fact two functionally distinct transcription factors, mediating their own response genes and physiological effects with little overlap. Selective ablation of PR-A in a mouse model, resulting in exclusive production of PR-B, unexpectedly revealed that PR-B contributes to, rather than inhibits, epithelial cell proliferation both in response to estrogen alone and in the presence of progesterone and estrogen. These results suggest that in the uterus, the PR-A isoform is necessary to oppose estrogen-induced proliferation as well as PR-B-dependent proliferation.

It was decades later that the secret behind this spectacular success became known.  The East German Sports Federation had, with the help of the Stasi, used Performance Enhancing Drugs or PEDs to ensure that their athletes gained international recognition by winning the Olympic events. This systematic plan had been initiated in 1974 as a means to guarantee international glory through the achievement of gold medals at the prestigious sporting event. Oral- Turinabol , a testosterone derivative was used extensively to improve muscle mass and cut down recovery time. This allowed the German athletes to train harder and longer than other world athletes. 

Currently, the SHBG test is not performed frequently or routinely. In many cases, health practitioners feel that the total testosterone , and perhaps free testosterone (as measured by a method called equilibrium dialysis), provides sufficient information. SHBG is ordered primarily when the total testosterone results do not seem to be consistent with clinical signs and symptoms , such as infertility, decreased sex drive, and erectile dysfunction in men or infertility , irregular menstrual periods, and excess facial and body hair in women.

Steroid hormone binding sites

steroid hormone binding sites

Currently, the SHBG test is not performed frequently or routinely. In many cases, health practitioners feel that the total testosterone , and perhaps free testosterone (as measured by a method called equilibrium dialysis), provides sufficient information. SHBG is ordered primarily when the total testosterone results do not seem to be consistent with clinical signs and symptoms , such as infertility, decreased sex drive, and erectile dysfunction in men or infertility , irregular menstrual periods, and excess facial and body hair in women.

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