Disease relevance of androstenedione

• Futhermore, extract from MtT/F4 tumors and "autonomous" pituitary tissue increased the 5alpha-reductase activity of hepatoma cells in the culture (HTC cells) at subsaturation concentrations of the substrate 4-androstene-3, 17-dione by decreasing the apparent Km of the enzyme [1].
• As compared with normal values for age, serum levels of dihydrotestosterone, free testosterone, and androstenedione were significantly decreased in patients with untreated vulvar lichen sclerosus [2].
• Androstenedione induction of these normal-term biochemical and endocrine changes accompanied by fetal membrane rupture, cervical dilatation and live delivery provides a rich opportunity to study the molecular and physiological mechanisms of both term and preterm labor in primates [3].
• Androstenedione production by residual ovarian stromal cells during reproductive life accounts for the epigenetic transmission of virilization in female spotted hyenas [4].
• IMPLICATIONS: Further research should focus on alternative endocrinologic mechanisms for risk associated with obesity and body fat distribution and for the biologic relevance of the increased risk associated with androstenedione in both premenopausal and postmenopausal disease [5].

Psychiatry related information on androstenedione

• Androstenedione and testosterone levels were higher among light to moderate drinkers compared to non-drinkers, although we only observe a significant trend with increasing levels of alcohol consumption for androstenedione [6].
• We evaluated the role of age, BMI, height, habitual physical activity, education, smoking, coffee and alcohol intake as predictors of serum testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, androstenedione, and SHBG concentrations in 100 healthy men 18-22 years old [7].
• During the critical period of brain differentiation, at the beginning of the second trimester of pregnancy, sex differences in T and A4 were found in amniotic fluid and not in maternal serum [8].
• This study explores the potential relationship between social behavior (aggression, dominance, and affiliation) and testosterone, androstenedione, and DHEA measurements in 5-year-old children while also analyzing the moderating effect of IQ on the hormone-behavior relationship [9].
• The responses of plasma testosterone (T), sex hormone-binding globulin (SHBG) binding capacity, androstenedione (A), and luteinizing hormone (LH) to 21 km of marching exercise and to sleep deprivation stress were studied in army recruits [10].

High impact information on androstenedione

• Patients with polycystic ovary syndrome responded to gonadotropin stimulation with normal to increased production of plasma estrogens and increased levels of androstenedione at 16 to 24 hours (P less than 0.05) [11].
• Markedly elevated basal plasma levels of androstenedione, estrone, and testosterone were regulated by gonadotropin but not by ACTH [12].
• 4OHA also inhibited the androstenedione induced maternal endocrine and fetal membrane biochemical changes, and alteration of myometrial activity patterns [13].
• In the present study, continuous infusion of androstenedione to 0.8 gestation monkeys resulted in the premature occurrence of labor-type myometrial activity and increases in maternal plasma estrogen, oxytocin and amnion fibronectin concentrations similar to those measured at normal-term labor [3].
• The limited aromatase activity may allow the hyena placenta to convert high circulating concentrations of androstenedione to testosterone, which results in virilization of the fetal external genitalia and possibly destruction of fetal ovarian follicles [4].

Chemical compound and disease context of androstenedione

• In the three siblings with gynecomastia, the transfer constant of conversion of androstenedione to estrone (i.e., the fraction of plasma androstenedione that was converted to estrone as measured in the urine) was 10 times that of normal persons [14].
• Plasma oestradiol-plus-oestron (E2 + E1), follicle-stimulating hormone (F.S.H.), luteinising hormone (L.H.), androstenedione (A2), and dehydroepiandrosterone sulphate (D.S.) were measured in 33 breast-cancer patients before and after adjuvant chemotherapy [15].
• Cirrhosis induced by carbon tetrachloride was also associated with greatly decreased activity of the microsomal cytochrome P450-independent 17 beta-oxidoreductase, an enzyme that catalyzes the conversion of androstenedione to testosterone [16].
• The source of this increased estrogen appears to be extragonadal metabolism of the prehormone androstenedione, which increases 3- to 4-fold in proportion to the obesity [17].
• The effect of treatment with the aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA) on the peripheral conversion of androstenedione to estrone has been examined in eight postmenopausal women with advanced breast cancer [18].

Biological context of androstenedione

• Mean (SE) changes in the AUC for serum estradiol concentrations were 4% (6%), 42% (12%), and 128% (24%) in the groups receiving 0, 100, and 300 mg/d of androstenedione, respectively [19].
• A new understanding of the endocrinology of menopause is that women, at menopause, are not only lacking estrogens resulting from cessation of ovarian activity but have also been progressively deprived for a few years of androgens and some estrogens originating from adrenal DHEA and androstenedione (4-dione) [20].
• Impaired hepatic elimination of androstenedione by hydroxylation may indirectly enhance extrahepatic aromatization of the androgen [21].
• The plasma concentrations of dehydroepiandrosterone, androstenedione, and dehydroepiandrosterone sulfate decrease during the first year of life, remain low during childhood, and then increase during adrenarche [22].
• The proximal androstenedione is positioned such that the alpha-face of carbon-6 is closest to the heme iron, and the second steroid molecule is positioned 5.5 A distal in the active site [23].

Anatomical context of androstenedione

• Several naturally occurring and synthetic flavones were found to inhibit the aromatization of androstenedione and testosterone to estrogens catalyzed by human placental and ovarian microsomes [24].
• CONCLUSIONS: Androstenedione supplementation does not increase serum testosterone concentrations or enhance skeletal muscle adaptations to resistance training in normotestosterogenic young men and may result in adverse health consequences [25].
• The increase of the mean cross-sectional area of type 2 muscle fibers was also similar in androstenedione (4703 [471] vs 5307 [604] mm2; P<.05) and placebo (5271 [485] vs 5728 [451] mm2; P<.05) groups [25].
• In granulosa cells, androstenedione is converted to estradiol by the aromatase P450 enzyme system [26].
• LH acts on theca cells via cAMP ro regulate both P450scc and P450(17) alpha mRNA levels, leading to increased biosynthesis of androstenedione [26].

Associations of androstenedione with other chemical compounds

• Hyena ovarian tissues incubated in vitro produced large quantities of the steroid hormone precursor androstenedione [4].
• DESIGN: Randomized controlled trial of androstenedione, open-label trial of 19-norandrostenedione, and mass spectrometry of androstenedione preparations, conducted between October 1998 and April 2000 [27].
• Estrogen, progesterone, and delta 4-androstenedione were measured in FF by radioimmunoassay [28].
• The precursors--namely, progesterone, pregnenolone, 17 alpha-progesterone, 17 alpha-hydroxypregnenolone, androstenedione, and dehydroepiandrosterone--caused a 2- to 3 1/2-fold enhancement of guanylate cyclase activity in rat liver, kidney, skeletal muscle, and ventral prostate at a concentration of 1 microM [29].
• Here, we report that androgens, such as the aromatizable androstenedione and the non-aromatizable 5alpha-dihydrotestosterone, inhibit MCF-7 cell proliferation [30].

Gene context of androstenedione

• MCF-7/CA cells overexpressing HER-2 showed a >2-fold increase in estrogen receptor (ER)-mediated transcriptional reporter activity upon treatment with androstenedione compared with vector-only control MCF-7/CA cells [31].
• In conclusion, the present study demonstrated a potent inhibitory effect of CRF on LH-stimulated dehydroepiandrosterone and androstenedione production that appears to be mediated through the reduction of P450c17 gene expression [32].
• In time-course studies, significant stimulation of the conversion of androstenedione to estrogens by hIL-1 beta could be detected as early as after 4 h of treatment and persisted for at least 24 h [33].
• GC were isolated from the ovaries of 26-day-old Sprague-Dawley rats, and were cultured (60,000 GC/well) in 96-well plates in the presence and absence of ovine FSH (0.001-100 ng/ml) and androstenedione (0.1 microM), with and without recombinant murine leptin (0.1-100 ng/ml) for 48 h [34].
• The role of SR-BI and ABCA1 in androstenedione production was also examined by treating cells with anti-SR-BI and 2-hydroxypropyl-beta-cyclodextrin in the presence and absence of human chorionic gonadotropin and/or human HDL(3) [35].

Analytical, diagnostic and therapeutic context of androstenedione

• Androstenedione MCR was determined during constant intravenous infusion of [3H]androstenedione, and the resultant radiolabeled steroids present in plasma were separated by thin layer chromatography [36].
• After 6 mo of adjuvant chemotherapy the premenopausal patients, 11 of whom had become amenorrhoeic, showed striking reductions in plasma E2 + E1 and A2 and elevations in plasma L.H. and F.S.H. Further changes were evident after 12 mo of treatment [15].
• Testosterone formation from androstenedione was noted in all studies using both homogenates and cell cultures [37].
• The metabolic clearance rates of other steroids such as hydrocortisone, medroxyprogesterone acetate, and androstenedione, and estrone are not altered by aminoglutethimide [38].
• Site-directed mutagenesis was then carried out at two sites: one at a region that aligns with the bend in the I-helix of cytochrome P-450CAM and the other at a glutamate (Glu302) just N-terminal of this bend, which is predicted to be in close proximity to the C2-position of the androstenedione substrate [39].

References