A large proportion of androgens in men (40%), and the majority of estrogens in women (75% before menopause and close to 100% after menopause), are synthesized in peripheral target tissues from precursor steroids of adrenal origin. The genes encoding the enzymes responsible for the formation and metabolism of androgens and estrogens are expressed in a large series of peripheral tissues, thus providing the basis for a promising new area in hormone action, namely intracrinology. These steroidogenic and steroid metabolizing enzymes should become a major target of novel therapies for steroid-sensitive diseases, particularly breast and prostate cancer.
Menopause is the cessation of ovarian function, with loss of reproductive hormone production and irreversible loss of fertility. It is a natural part of reproductive aging. The physiology of the menopause is complex and incompletely understood. Globally, menopause occurs around the age of 49 years, with geographic and ethnic variation. The hormonal changes of the menopause transition may result in both symptoms and long-term systemic effects, predominantly adverse effects on cardiometabolic and musculoskeletal health. The most effective treatment for bothersome menopausal symptoms is evidence-based, menopausal hormone therapy (MHT), which reduces bone loss and may have cardiometabolic benefits. Evidence-based non-hormonal interventions are also available for symptom relief. Treatment should be individualized with shared decision-making. Most MHT regimens are not regulator approved for perimenopausal women. Studies that include perimenopausal women are needed to determine the efficacy and safety of treatment options. Further research is crucial to improve menopause care, along with research to guide policy and clinical practice.
To study the relationship between the steroid concentration in the endometrium, in serum, and the gene expression level of steroid-metabolizing enzymes in the context of endometrial receptivity in in vitro fertilization (IVF) patients.
Case-control study of 40 IVF patients recruited in the SCRaTCH study (NTR5342), a randomized controlled trial investigating pregnancy outcome after “endometrial scratching.” Endometrial biopsies and serum were obtained from patients with a first failed IVF cycle randomized to the endometrial scratch in the midluteal phase of the natural cycle before the next fresh embryo transfer during the second IVF cycle.
University hopsital.
Twenty women with clinical pregnancy were compared with 20 women who did not conceive after fresh embryo transfer. Cases and controls were matched for primary vs. secondary infertility, embryo quality, and age.
None.
Steroid concentrations in endometrial tissue homogenates and serum were measured with liquid chromatography-mass spectrometry. The endometrial transcriptome was profiled by RNA-sequencing, followed by principal component analysis and differential expression analysis. False discovery rate-adjusted and log-fold change >|0.5| were selected as the threshold for differentially expressed genes.
Estrogen levels were comparable in both serum (n = 16) and endometrium (n = 40). Androgens and 17-hydroxyprogesterone were higher in serum than that in endometrium. Although steroid levels did not vary between pregnant and nonpregnant groups, subgroup analysis of primary women with infertility showed a significantly lower estrone concentration and estrone:androstenedione ratio in serum of the pregnant group (n = 5) compared with the nonpregnant group (n = 2). Expression of 34 out of 46 genes encoding the enzymes controlling the local steroid metabolism was detected, and estrogen receptor β gene was differentially expressed between pregnant and nonpregnant women. When only the primary infertile group was considered, 28 genes were differentially expressed between pregnant and nonpregnant women, including HSD11B2, that catalyzes the conversion of cortisol into cortisone.
Steroidomic and transcriptomic analyses show that steroid concentrations are regulated by the local metabolism in the endometrium. Although no differences were found in endometrial steroid concentration in the pregnant and nonpregnant IVF patients, primary women with infertility showed deviations in steroid levels and gene expression, indicating that a more homogeneous patient group is required to uncover the exact role of steroid metabolism in endometrial receptivity.
We developed a microplate enzyme immunoassay (EIA) to measure dehydroepiandrosterone sulfate (DHEAS) in the blood, urine, and feces of Japanese macaques and evaluated the relationship between serum DHEAS and excreta DHEAS. Our DHEAS EIA using heterological DHEA derivatives conjugated with enzyme was highly sensitive, and linearities and recoveries for all matrices of Japanese macaques were reliable. For the biological evaluation of the metabolism of DHEAS in Japanese macaques, dissolved DHEAS was injected into the subjects, and consecutively collected serum, urine, and fecal samples were analyzed. The peaks of serum DHEAS were observed 6 h after the administration, while those of urine and feces were observed after 24 h. The fluctuation of those in urine and feces were significantly correlated with serum DHEAS levels. In addition, we measured pregnanediol-glucuronide (PdG), and estrone-conjugate (E1C) in urine and fecal samples to investigate the effects of administrated DHEAS on these progesterone and estrogen metabolites. The peak of PdG was observed 24 h after administration, then declined sharply. The concentration of E1C increased 1 week after administration in two out of three subjects. Our results suggest that measuring urinary and fecal DHEAS with our EIA provides a non-invasive alternative to assessing DHEAS levels in the serum of Japanese macaques.
An apparent vitamin D paradox, characterized by lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher bone mineral density, is present in black population. In contrast, blacks have higher serum 1,25-dihydroxyvitamin D (1,25(OH)2D) levels. The effect of 1,25(OH)2D on the skeleton is not fully understood. We examined serum 25(OH)D, 1,25(OH)2D and bone histomorphometry in 50 black and white women (25 each) matched for age, menstrual status, and BMI. Histomorphometric indices related to bone structure, remodeling and mineralization were measured in cancellous bone in iliac bone biopsies. Data analyses led to the following results: 1) serum 25(OH)D was significantly lower and 1,25(OH)2D was significantly higher in black than in white women, but neither blacks nor whites revealed significant correlation between these two vitamin D metabolites. 2) there was no significant difference in PTH levels between blacks and whites. 3) except for greater trabecular thickness (Tb.Th) in blacks, there were no significant differences in other histomorphometric variables between the two ethnic groups. 4) osteoid surface (OS/BS), unlabeled osteoid surface (ulOS/BS), and osteoblast surface (ObS/BS) significantly correlated with serum 1,25(OH)2D levels. We conclude that lower serum 25(OH)D levels in blacks do not impair bone structure and remodeling, nor decrease bone mineralization. Higher serum 1,25(OH)2D levels in blacks may help preserve bone mass by stimulating bone formation via increasing osteoblast number and function, but moderately inhibit terminal bone mineralization as shown by higher ulOS/BS.
Curcumin is a phytochemical derived from the spice turmeric that is reported to have therapeutic effects. We are studying the enzyme steroid sulfatase (STS), which removes the sulfate group from inactive steroid hormones in peripheral tissues and we were interested in the effect of curcumin on STS activity due to its structural composition (polyphenolic). We sought to determine if curcumin affects STS activity in two model systems, rat liver and NIH-3T3 mouse fibroblast cells. STS assays were performed on tissue extracts of rat liver, and on NIH-3T3 microsomes and cells, with and without curcumin. Male and female rat liver extracts contained substantial amounts of STS activity, with males averaging higher (4–11 %) levels. Estradiol inhibited STS activity in livers of both sexes at 20 and 10 µM. Curcumin acted as a competitive inhibitor of STS activity in rat liver extracts, with a Ki of 19.8 µM in males and 9.3 µM in females. Curcumin also inhibited STS activity in NIH-3T3 microsomes at both 20 µM and 10 µM, and in whole NIH-3T3 cells at 20 µM. These data are the first to demonstrate STS inhibition by curcumin. Inhibition of STS results in lower active steroid hormone (estrogens and androgens) levels in tissues, possibly altering modulation of immune responses by these steroids.