Cancer of the Breast
Jennifer L. Kelsey, Nancy G. Hildreth in Breast and Gynecologic Cancer Epidemiology, 2019
Finally, a theory recently proposed by Siiteri et al.304 involves the role of sex hormone binding globulin (SHBG), a protein present in human sera which is capable of binding with high affinity to both androgens and estrogens. Since SHBG levels are inversely correlated with the level of free estradiol (E2) in the serum,304–306 it is possible that this protein influences the availability of estrogen to target cells. Reduced serum SHBG levels have been found to be associated with excess body weight,304,307 so that this hypothesis would be consistent with obesity as a risk factor for breast cancer in postmenopausal women. Since individuals could have similar total serum E2 levels but different amounts of free E2, Siiteri et al.304 state that this hypothesis could account for the failure of most studies to find differences in serum estrogen levels when comparing women with breast cancer to controls or women at high risk to those at low risk of breast cancer. The authors suggest that future studies focus on identifying factors that are associated with SHBG levels and on determining whether the level of this protein is reduced in women with a family history of breast cancer.
Pattern hair loss: Pathogenesis, clinical features, diagnosis, and management
Jerry Shapiro, Nina Otberg in Hair Loss and Restoration, 2015
Sex hormone–binding globulin (SHBG) is the main transport protein for circulating testosterone and estradiol. SHBG is produced in liver cells and to some degree in the brain, uterus, placenta, and vagina. SHBG levels are regulated by a delicate balance of inhibiting and enhancing factors. High androgen levels decrease the production of SHBG, whereas estrogen and thyroxine increase SHBG. Moreover, IGF can suppress SHBG. Only unbound testosterone and estradiol are biologically active; therefore, the lower the SHBG blood levels, the higher the bioavailability of androgens. Conditions in which low SHBG occurs include polycystic ovary syndrome, diabetes, and hypothyroidism. Vexiau et al. [77] were able to show that SHBG levels are inversely correlated to the degree of hair loss in women with FPHL.
Androgen production over the female life span
Barry G. Wren in Progress in the Management of the Menopause, 2020
Although the plasma concentration of androgen determines the amount of hormone potentially available for action at target tissues, its rate of transport into cells is largely determined by a specific plasma binding protein (sex hormone-binding globulin, SHBG) which binds testosterone at such high affinity that only 1-2% of the hormone is free to act on the target cell. This free T level, which is usually expressed as the free T index (calculated from the levels of total T and SHBG) is a far better index of ancirogenicity than the total T Under certain circumstances such as hyperthyroidism and pregnancy, SHBG is increased and this can have effects on the free level of plasma T Moreover, estrogen administration, e.g. hormone replacement therapy (HRT) may increase SHBG levels and result in decreased free T levels which may have significance for the well-being of these patients, as it could be that T plays an important role in this process. Thus, the plasma level of free T is a variable fraction of the total hormone concentration and depends on the amount of binding protein present.
Inverse association of testosterone and sex hormone binding globulin levels with leukocyte count in middle-aged and elderly men
Published in The Aging Male, 2018
A low testosterone level has been traditionally considered to be a marker of male hypogonadism and is also related to quality of life issues [1–4], but recent epidemiological evidence has highlighted the significance of low testosterone level in male patients with cardiometabolic diseases such as coronary heart disease, metabolic syndrome, and type 2 diabetes through cross-sectional and longitudinal studies [5–12], which are closely related to subclinical atherosclerosis or autonomic imbalances [13,14]. Sex hormone-binding globulin (SHBG), produced mainly from the liver, is the primary transport glycoprotein for sex steroid hormones and modulates their bioavailability in peripheral target tissues. A growing body of previous studies documented the potential metabolic significance of SHBG in addition to controlling free sex hormone levels. A low SHBG level has been inversely associated with increased risk of type 2 diabetes and metabolic syndrome, independent of sex hormones in both sexes [5–9,15,16].
Common markers of testicular Sertoli cells
Published in Expert Review of Molecular Diagnostics, 2021
Xu You, Qian Chen, Ding Yuan, Changcheng Zhang, Haixia Zhao
ABP is a type of heterodimeric glycoprotein with a molecular weight of 85 kDa that is secreted primarily by Sertoli cells into the bloodstream and seminiferous tubule lumen [135,136], accounting for about 0.01% of total testicular proteins. ABP has a high affinity for testosterone secreted by Leydig cells and regulates spermatogenesis. It has been reported that ABP levels in serum and testicular interstitial fluid of SD rats are highest 30 days after birth, sharply decline by 40 days, and then gradually increase to 100 days of age [137]. Notably, sex hormone-binding globulin (SHBG) in the blood–another glycoprotein exhibiting high affinity for hormones–can also compete with ABP to bind and transport androgens in the blood into their target tissues and cells. However, SHBG also has a high affinity for other hormones, such as estrogens, and is associated with several pathological conditions, including endometrial cancer, ovarian dysfunction, breast cancer, nodal metastases, preeclampsia, osteoporosis, Alzheimer’s disease, diabetes mellitus, and some cardiovascular diseases [138,139]. Thus, compared with SHBG, only ABP is currently used as a critical indicator in the study of the physiologic, pathologic, and hormonal regulation of the testis (including Sertoli cells) [135]; it is also used as a biologic marker of Sertoli cell secretory function [140–142].
Disruptions in the reproductive system of female rats after prenatal lipopolysaccharide-induced immunological stress: role of sex steroids
Published in Stress, 2019
V. M. Ignatiuk, M. S. Izvolskaya, V. S. Sharova, S. N. Voronova, L. A. Zakharova
The formation of cyst-like structures after estradiol antagonist treatment of prenatally LPS-treated females also evidences that the disruption of sex steroid balance during PND induces disorders in folliculogenesis. Polycystic ovarian syndrome is associated with cyst formation due to abnormal development of antral follicles. It can be induced with testosterone exposure during the perinatal period (Padmanabhan & Veiga-Lopez, 2013). The main diagnostic characteristics of this disorder are increased production of LH by the pituitary gland and of testosterone in the ovaries and adrenal glands. The latter is associated with a disruption of aromatase synthesis (CYP19) in granulosa cells (Rosenfield & Ehrmann, 2016). Aromatase is the enzyme catalyzing the conversion of testosterone into estrogens (Takayama et al., 1996). Polycystic ovarian syndrome is also associated with increased production of testosterone by theca cells (Nelson et al., 2001) and adrenal hyperplasia in perinatally androgenized animals. Testosterone synthesis in females also takes place in muscle and adipose tissues (Cadagan, Khan, & Amer, 2014; Payne & Hales, 2004). Moreover, testosterone in circulating blood binds to a greater degree with proteins, particularly with albumins and sex hormone-binding globulin (Laurent et al., 2016).