Disease relevance of folliculin

• Patients with liver disease had significantly elevated plasma levels of E1 (74.2 +/- 8.0 SE versus 26.0 +/- 1.7 pg per ml, P less than 0.001), E2 (29.3 +/- 2.2 versus 23.3 +/- 2.0 pg per ml, P = less than 0.05), and E3 (11.5 + 1.9 versus 6.5 +/- 0.7 pg per ml, P less than 0.01) [1].
• The high E1/A ratio in Latina women was not associated with a high breast cancer incidence; in fact Latina women had the lowest breast cancer incidence in the cohort observed so far [2].
• The present findings, together with our previous data demonstrating an increased adrenal secretion of the E1 precursor A in response to ACTH in obese women, suggests that the adrenal cortex in overweight women may further enhance the estrogenic milieu of these women [3].
• Prolactin (PRL), human placental lactogen (hPL), the beta-subunit of human chorionic gonadotropin (betahCG), testosterone (T), estrone (E1), and estradiol (E2) were measured in blood samples from 45 patients with testicular tumors, 27 of whom had gynecomastia at some stage of their disease [4].
• Finally, mapping the genetic mutations into the ES structure provides an explanation for the loss of enzyme function in X-linked ichthyosis [5].

High impact information on folliculin

• The rat OB cells also showed 17 beta-HSD activity, with the predominant metabolism in all three cell lines being estrone (E1) to E2 [6].
• Type 1 17 beta-HSD, which encodes the enzyme responsible for the conversion of E1 to E2 in the placenta and ovary, was expressed in the subcutaneous abdominal and intra-abdominal adipose tissue of women, but the messenger RNA transcripts were predominantly incompletely spliced and therefore unlikely to encode an active protein [7].
• There were no differences in ff E1 or E2 levels at any stage of oocyte maturation, except that the mean ff E2 concentration was significantly (P less than 0.05) lower in ff containing dg oocytes [2,474 +/- 1,435 (+/- SE) nmol/L] than in those containing the other oocyte stages [8].
• AR was expressed either as femtomoles of E2 per microgram DNA (ARE2) or as total aromatized metabolites (ART = E1 + E2 + 16 alpha-OHE1 + E3 + epiE3/microgram DNA) [9].
• These results indicate that the equine estrogens bind to SHBG and albumin in a manner similar to that of E1 and E2, and that the low MCR of EqS reported previously may be due to its binding to albumin [10].

Biological context of folliculin

• The attractivity of female Japanese macaques increased significantly during the follicular and periovulatory phases of the ovarian cycle, when E1 levels are peaking and PdG levels drop to baseline [11].
• Primary exposure to E1 increased vitellogenesis after secondary exposure to MXCL only marginally [12].
• At 2 months, while partially breastfeeding, FSH, E2 and E1 were closer to menopausal range (68 IU/l, 136 and 70.2 pmol/l respectively), and hormone replacement was started [13].
• Buildup of E1 and E2 overwhelms the competitive binding of tamoxifen to the estrogen receptor, resulting in tumor progression [14].
• Examination of the ES active site reveals substrate-specific interactions previously identified in another steroidogenic enzyme [5].

Anatomical context of folliculin

• The strio-amygdaloid complex of both sexes synthesized more E1 per unit weight than the preoptic-hypothalamic area (POA-HTH) or other forebrain structures [15].
• No other neural or non-neural tissues, including mid- and hindbrain structures, testis, and ovary, synthesized detectable quantities of E1 in our system [15].
• Thus, the rat and mouse preimplantation embryo could regulate the E1- to -E2 ratio in the embryos and in their environment [16].
• Isolated carp hepatocytes were first exposed (primary exposure) to 50 or 100 microM of either methoxychlor (MXCL) or bisphenol A (BPA), different concentrations of estrone (E1; 1 or 10 nM) or 17beta-estradiol (E2; 0.1 or 1 nM) for 2 days [12].
• These data indicate that rapid absorption of E1 and E2 occurs through irradiated vaginal mucosa [17].

Associations of folliculin with other chemical compounds

• The binding constants of some estrogens and androgens to SHBG at 37 C determined by competitive Scatchard analysis using DEAE filter assay and [3H]5 alpha-DHT were 0.15, 0.07, 0.22, 0.29, 2.70, and 4.53 (X 10(9) M-1) for Eq, E1, 17 beta-Eq, E2, T, and 5 alpha-DHT, respectively [10].
• The immunoprecipitation method efficiently removed 99% of radiolabeled E2 and estrone (E1) from human serum [18].
• In Xenopus laevis oocytes expressing OATP1A2, the uptake of the model substrate, estrone-3-sulfate (ES), was enhanced 30-fold compared with uninjected oocytes [19].
• Simultaneous determinations of 17 beta-estradiol (E2), estrone (E1), and progesterone (P) in plasma and tubal tissue were carried out by specific radioimmunoassay [20].
• Comparing the EC50 values in bream hepatocytes: EE2 (0.1-0.2 microM) < E1 (0.6-0.2 microM) < E2 (1.9 microM) with those of carp hepatocytes EE2 (0.03-0.06 microM) < E2 (0.3 microM) approximately E1 (0.2-0.3 microM) we found differences in sensitivity and ranking of the estrogenic potency of E2 and E1, indicating interspecies differences [21].

Gene context of folliculin

• MRP2 showed the highest efflux clearance of EG among these efflux transporters, whereas BCRP-mediated clearance of ES was the highest in these double transfectants [22].
• In unadjusted models, logged free and total testosterone, DHEA, and DHEAS related to higher functioning in at least one cognitive domain; logged FSH, SHBG, and LH related to lower functioning in at least one cognitive domain; and logged E1, CRT, and PRL were not significant [23].
• While ARSA, ARSB, and PAS are water-soluble enzymes, ES has a hydrophobic domain and is presumed to be bound to the endoplasmic reticulum membrane [5].
• Crystal structures of three human sulfatases, arylsulfatases A and B (ARSA and ARSB) and C, also known as steroid sulfatase or estrone/dehydroepiandrosterone sulfatase (ES), have been determined [5].
• Decreasers had mean values of serum PRL, plasma E1, DHEA-S, and 17-OHP higher than nonresponders (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)[24]

Analytical, diagnostic and therapeutic context of folliculin

• In experiments in which supraphysiologic concentrations of E2 and E1 to human serum, all of the immunoreactive estrogens were still removed by the immunoprecipitation protocol [18].
• The age- and weight-adjusted ethnic specific E1/A ratios x 100 among women without oophorectomy were 7.92 in African-Americans, 8.22 in Japanese, 10.73 in Latinas and 9.29 in non-Latina Whites (P=0.09) [2].
• The E2-EQ(C) for E1 and E2 were on the same order as the estrogenic activity determined by the bioassay (E2-EQ(B)) [25].
• This study examines the ability of Arctic charr (Salvelinus alpinus) embryos to metabolize tritiated androstenedione (A4), testosterone (T), 17 beta-estradiol (E2), and estrone (E1) in vitro; the metabolic products were separated by HPLC [26].
• The objective of this study was to determine the effect of passive immunization against estrone (E1), estradiol (E2) or estrogens (nonspecific; Ens) on ovulation rate and kidding rate in Angora does [27].

References