In this randomized controlled trial with caffeinated and decaffeinated coffee interventions, we did not find evidence of a consistent effect on SHBG levels in over- weight men or women. This contrasts with the beneficial effects of coffee consumption on adiponectin and fetuin- A levels previously reported in this trial , suggesting that the SHBG level is not the major intermediate of the putative effect of coffee consumption on a lower risk of T2DM. Our findings necessitate further examination in a larger intervention trial of the effects of coffee on sex hormones to elucidate if this is a potential intermediary Table 3 Sex hormone-binding globulin and endogenous sex hormones by treatment group at week 4 and week 8 in women
Hormone-binding protein (HBP) is a kind of soluble carrier protein and can selectively and non-covalently interact with hormone. HBP plays an important role in life growth, but its function is still unclear. Correct recognition of HBPs is the first step to further study their function and understand their biological process. However, it is difficult to correctly recognize HBPs from more and more proteins through traditional biochemical experiments because of high experimental cost and long experimental period. To overcome these disadvantages, we designed a computational method for identifying HBPs accurately in the study. At first, we collected HBP data from UniProt to establish a high-quality benchmark dataset. Based on the dataset, the dipeptide composition was extracted from HBP residue sequences. In order to find out the optimal features to provide key clues for HBP identification, the analysis of various (ANOVA) was performed for feature ranking. The optimal features were selected through the incremental feature selection strategy. Subsequently, the features were inputted into support vector machine (SVM) for prediction model construction. Jackknife cross-validation results showed that 88.6% HBPs and 81.3% non-HBPs were correctly recognized, suggesting that our proposed model was powerful. This study provides a new strategy to identify HBPs. Moreover, based on the proposed model, we established a webserver called HBPred, which could be freely accessed at http://lin-group.cn/server/HBPred.
We have investigated the basis of androgen resistance in seven unrelated individuals with complete testicular feminization or Reifenstein syndrome caused by single amino acid substitutions in the hormone-binding domain of the androgen receptor. Monolayer-binding assays of cultured genital skin fibroblasts demonstrated absent ligand binding, qualitative abnormalities of androgen binding, or a decreased amount of qualitatively normal receptor. The consequences of these mutations were examined by introducing the mutations by site- directed mutagenesis into the androgen receptor cDNA sequence and expressing the mutant cDNAs in mammalian cells. The effects of the amino acid substitutions on the
A single point mutation in the growth hormone (GH) receptor gene generating a Phe-->Ser substitution in the extracellular binding domain of the receptor has been identified in one family with Laron type dwarfism. The mutation was introduced by site-directed mutagenesis into cDNAs encoding the full-length rabbit GH receptor and the extracellular domain or binding protein (BP) of the human and rabbit GH receptor, and also in cDNAs encoding the full length and the extracellular domain of the related rabbit prolactin (PRL) receptor. All constructs were transiently expressed in COS-7 cells. Both wild type and mutant full-length rabbit GH and PRL receptors, as well as GH and prolactin BPs (wild type and mutant), were detected by Western blot in cell membranes and concentrated culture media, respectively. Immunofluorescence studies showed that wild type and mutant full-length GH receptors had the same cell surface and intracellular distribution and were expressed with comparable intensities. In contrast, all mutant forms (full-length receptors or BPs), completely lost their modify the synthesis ligand. These results clearly demonstrate that this point mutation (patients with Laron syndrome) does not modify the synthesis or the intracellular pathway of receptor proteins, but rather abolishes ability of the receptor or BP to bind GH and is thus responsible for the extreme GH resistance in these patients.
Traditionally, the classical description of bilateral sclerocystic ovaries in women presenting with anovulation or hirsutism, first described in 1935 by Stein and Leventhal, has been the principal diagnostic criteria for polycystic ovary syndrome (PCOS). The associated endocrine abnormalities of a raised luteinising hormone (LH) and testosterone (T) level have become additional indices (MacArthur et al.l958. Yen 1970, Gambrell et al.l973. Rebar et al. 1976, Yen 1980) and in some studies are considered more important than the morphological appearance of the ovaries. Results from subsequent reports using clinical, endocrine and morphological features (both ovarian biopsy and pelvic ultrasound) as diagnostic criteria has brought the realisation that PCOS is a heterogeneous condition (Goldzeiher and Green 1962, Jeffcoate 1963, Givens 1977,1984, Yen 1980) with a spectrum of clinical and biochemical presentations. The clinical presentation of PCOS includes women who are anovulatory but not hirsute as well as those who have ovulatory cycles and are hirsute. The majority of women with polycystic ovaries (PCO) on ultrasound have a raised LH and/or testosterone level (Adams et al. 1985,86, Franks et al. 1989, Conway et al. 1989). There is evidence that PCOS is a familial condition (Hague et al. 1988) but the clinical and biochemical presentation of the syndrome may be determined by environmen tal as well as genetic factors.
Reproductive and thyroid hormones play an essential role in the maintenance of pregnancy and the develop- ment of the fetus [12–16], therefore pregnancy is a vulnerable window for endocrine disruption due to the varying levels of hormones involved in the growing organism . Endocrine disrupting chemicals could act through several pathways, including hormone synthesis, regulation, transport and metabolism, and/or inter- ference with receptors. Phenols and parabens have estro- genic and androgenic properties [1, 18–20], but few human studies have looked into the effect of these che- micals on maternal hormones during pregnancy. Most existing studies in this area use smaller study popula- tions or only examined a single time point in pregnancy, which do not capture the changing hormone levels and high variability of phenols and paraben exposure during pregnancy. Furthermore, no or few studies explored the associations between these chemicals and maternal testosterone, corticotropin-releasing hormone (CRH), sex hormone-binding globulin (SHBG) and estriol, all of which play essential roles in maintaining healthy pregnancies. Given the growing evidence of the endocrine disrupt- ing effects of phenols and parabens [18, 21–25], our aim was to study the relationships between phenols and parabens on reproductive and thyroid hormones in our ongoing cohort of pregnant women in Puerto Rico. The study follows the women over multiple time points during pregnancy, providing more power than previous studies, and allows for the identification of potential windows of susceptibility. We previously reported early preliminary results on associations between select phe- nols and parabens with hormones in this Puerto Rican cohort . This manuscript is an update of our pre- vious results that utilizes a much larger sample size, includes additional hormones (estriol, testosterone, total triiodothyronine, and total thyroxine), as well as ad- ditional exposure biomarkers yet to be studied in detail (ethylparaben, BPS, BPF and triclocarban). Due to the lack of human health data, this study was exploratory in nature, with the exception of BPA, triclosan, methyl- paraben and propylparaben. We hypothesized a decrease in serum thyroid hormone levels in association with
Background and Objective: The hormonal responses are different, according to type, intensity and the duration of training. We aimed to compare the effect of endurance and resistance training in untrained men on the level sexual hormone including testosterone, estradiol, and on sex hormonebinding globulin (SHBG).
Liver fat is recognized as a separate and important contributor to metabolic disease development. The liver is an insulin responsive tissue that contributes significantly to both whole body insulin sensitivity and availability of sex steroids through the production of sex hormonebinding globulin (SHBG). Our objective was to describe the relationship between ectopic liver fat, insulin resistance, and hormonal profile in perimenopausal women. The Study of Women Across the Nation (SWAN) is a cross sectional multiethnic population of women recruited from multiple geographic areas during their perimenopausal years for longitudinal evaluation. A subset of women from SWAN (n=208) were evaluated from the Pittsburgh site as part of the SWAN-Heart study. Women had computed tomography scans to quantify visceral and subcutaneous adipose tissue, and liver fat. Adiposity measures, blood pressure, and menopausal stage, based on cycle irregularity, were recorded. Blood samples were collected and measured for hormonal and metabolic endpoints. We found in this overweight but healthy cohort that liver fat and SHBG were unaffected by menopausal stage or race. Both endpoints remained significantly associated with insulin after adjustment for adiposity. SHBG and liver fat had interactive effects on measured insulin concentration. Other sex hormones were not significantly associated with metabolic endpoints. Only liver fat accounted for differences in insulin across increasing SHBG quartiles, suggesting ectopic liver fat modifies SHBG. Both higher liver fat and lower SHBG have consequences for insulin sensitivity and the role of liver fat in modifying SHBG should be explored.
A recent study, which compared thyroid hormone regulation of S- and M-cone opsin enhancer ele- ments, supports this conclusion (30). The S-cone opsin enhancer was activated by CRX, a photorecep- tor-specific homeobox protein, and TR-β2–inhibited gene expression from this enhancer. In contrast, the M-cone enhancer activity was not activated by either TR-β2 or CRX; however, thyroid hormone treatment stimulated gene expression via this element. Thyroid hormone therefore has the potential to control opsin gene expression in the retina in much the same way as it affects myosin heavy chain α and β (MHC-α and MHC-β) gene expression in the myocardium (31): stimulating one gene product (M-cone opsin and MHC- α ), while reciprocally inhibiting a related gene product (S-cone opsin and MHC-β).
Corticotropin-releasing hormone (CRH), the principal neuropeptide regulator of pituitary ACTH secretion, is also produced at peripheral inflammatory sites, where it acts as a proinflammatory cytokine, and by the Leydig cell of the testis, where it exerts autocrine inhibition of testosterone biosynthesis. Because key ovarian functions, such as ovulation and luteolysis, represent aseptic inflammatory responses, and because the theca cell is the functional equivalent of the Leydig cell, we explored the CRH presence in the ovary, first, by specific CRH immunohistochemistry of adult cycling female Sprague-Dawley rat ovaries. We detected cytoplasmic immunoreactive CRH (IrCRH) in theca and stromal cells and in cells within the corpora lutea, at all phases of the estrous cycle. Using a specific
The control of gene transcription is usually mediated by transacting transcriptional factors that bind to upstream regulatory elements. As insulin regulates transcription of the growth hormone (GH) gene, we tested nuclear extracts from unstimulated and insulin-stimulated Chinese hamster ovarian (CHO) cells for binding to four human GH (hGH) gene promoter oligonucleotide fragments identified as target-binding sequences by DNAse I footprinting. Using a mobility shift assay, an insulin-induced DNA-binding protein was identified. This protein binds to two upstream overlapping oligonucleotide sequences. Binding activity is present at low levels in unstimulated CHO cells and is stimulated by insulin treatment with a time course suggesting that protein synthesis is required. Incubation of the cells with
The recent identification of riboswitches in eukaryotes has expanded the concept of the expression platform. In almost all cases bacterial riboswitch elements are located in the 5 ’ untranslated region of mRNAs  including TPP (thiamine pyrophosphate) binding riboswitches. TPP binding riboswitches have been identified in Arabi- dopsis thaliana and Neurospora Crassa [16,17]. In these two examples, the location of the riboswitch is different from prokaryotes suggesting divergence of the expres- sion platform despite conservation of the TPP binding sequence. In Arabidopsis the riboswitch is located in the 3’ untranslated region of the THIC gene, just 5’ of the polyA tail . The Neurospora TPP riboswitches are located within the first and second introns of the NMT1 and THI4 genes, respectively . In both Neurospora and Arabidopsis, ligand binding causes a conformational change and alternative splicing of the transcripts . In Neurospora, TPP-binding leads to intronic translation and a premature termination codon, whereas in Arabi- dopsis, TPP-binding causes splicing of the consensus polyadenylation sequence [17,18]. This leads to the pro- duction of several polyadenylation variants which have less stability than transcripts polyadenylated at the con- served site . Despite these radical departures from the model prokaryotic riboswitch expression platform, it remains that this singular example of a eukaryotic ribos- witch is involved in the regulation of a biosynthetic pathway . The mechanistic divergence between pro- karyotic and eukaryotic riboswitches leaves open the possibility that functional divergence has occurred as well. As life became more complex riboswitches could have evolved to play a broader role in signal perception, transduction, and integration.
Hypopituitarism is a clinical syndrome of deficiencies in one or more pituitary hormones of which adrenocortico- trophic hormone (ACTH) deficiency resulting in adrenal failure is the most serious and potentially life-threatening feature. ACTH deficiency can present as a part of generalized pituitary failure (multiple pituitary hormone deficiency, MPHD) or less commonly as an isolated entity. In the most severe cases, it can manifest acutely and dramatically as a life-threatening adrenal crisis with vas- cular collapse especially during an intercurrent illness while in other cases, the features are more subtle and the onset is gradual. It may also be diagnosed during assessment of pituitary axes as part of routine practice in those with pituitary tumours or following pituitary surgery or radiation therapy in otherwise well patients with little or no symptoms.
The modulation of cortisol-binding sites by stress is well documented in fish and other vertebrates. Prolonged exposure to stressful conditions, resulting in elevated levels of blood cortisol, causes a significant down-regulation of the putative receptor in certain tissues. This phenomenon has been observed in rainbow trout liver (Pottinger, 1990; Pottinger et al. 1994a) and coho salmon gill (Maule and Schreck, 1991; Shrimpton and Randall, 1994) and has been demonstrated to be a direct consequence of elevated levels of the steroid; down- regulation occurs in response to exogenously administered corticosteroid in otherwise unstressed fish (Pottinger, 1990; Maule and Schreck, 1991; Lee et al. 1992). In these previous studies, down-regulation has been manifested as a significant decline (by as much as 85 %) in the number of measurable cortisol-binding sites relative to a reasonably stable number of sites in unstressed fish (Pottinger et al. 1994a). In contrast, a twofold or greater increase in the number of triamcinolone- acetonide-binding sites in leucocytes from the spleen and anterior kidney was observed in coho salmon subjected to acute or chronic stress (Maule and Schreck, 1991). In the present study, no change in the number of erythrocyte binding sites was observed during stress; the number of binding sites per cell remained relatively constant. However, a significant increase in the number, or up-regulation, of binding sites was observed in those fish that were maintained as controls, under conditions which were as far as possible free from stressful stimuli. These changes in binding site abundance appear to be related to the nutritional status of the fish. Exposure of fish to stressful conditions normally results in loss of appetite and cessation of feeding. Food was therefore withheld from both control and confined fish during the stress experiments to eliminate this possible source of variation. We subsequently observed that withdrawal of food from otherwise unstressed fish resulted in a significant increase in the number of erythrocyte cortisol-binding sites. There was no change in the number of binding sites in fish that were fed. Therefore, stress appears to oppose the increase in the number of erythrocyte cortisol-binding sites induced by starvation and observed in otherwise unstressed fish. It is unlikely that a situation could arise in which chronically stressed fish continued to feed normally; the absence of a change in the number of erythrocyte cortisol-binding sites observed in fish stressed by confinement might reasonably be assumed to represent the situation pertaining during periods of ‘natural’ stress and, therefore, is likely to be of adaptive significance.
As noted in previous studies, the lemon balm affects the blocking of TSH binding to the receptor by influencing the hormone and the receptor itself. It also prevents the production of cyclic AMP stimulated by TSH receptor antibodies. Conventionally, lemon balm is used to treat hyperthyroidism symptoms such as tachycardia, insomnia, and hyperactivity. The M. officinalis extract increases the secretion of TRH and TSH levels and subsequently increases T3 and T4 levels. The increase in T3 and T4 can ultimately lead to a decrease in TSH levels through negative feedback.  A. marmelos