Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042755 (masculinization)
 2,562 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aromatase enzyme complex catalyzes the conversion of androgens to estrogens in a wide variety of tissues, including the ovary, testis, placenta, brain, and adipose tissue. Only a single human gene encoding aromatase P450 (CYP19) has been isolated; tissue-specific regulation is controlled in part by alternative promoters in a tissue-specific manner. We report a novel mutation in the CYP19 gene in a sister and brother. The 28-yr-old XX proband, followed since infancy, exhibited the cardinal features of the aromatase deficiency syndrome as recently defined. She had nonadrenal female pseudohermaphrodism at birth and underwent repair of the external genitalia, including a clitorectomy. At the age of puberty, she developed progressive signs of virilization, pubertal failure with no signs of estrogen action, hypergonadotropic hypogonadism, polycystic ovaries on pelvic sonography, and tall stature. The basal concentrations of plasma testosterone, androstenedione, and 17-hydroxyprogesterone were elevated, whereas plasma estradiol was low. Cyst fluid from the polycystic ovaries had a strikingly abnormal ratio of androstenedione and testosterone to estradiol and estrone. Hormone replacement therapy led to breast development, menses, resolution of ovarian cysts, and suppression of the elevated FSH and LH values. Her adult height is 177.6 cm (+2.5 SD). Her only sibling, an XY male, was studied at 24 yr of age. During both pregnancies, the mother exhibited signs of progressive virilization that regressed postpartum. The height of the brother was 204 cm (+3.7 SD) with eunuchoid skeletal proportions, and the weight was 135.1 kg (+2.1 SD). He was sexually fully mature and had macroorchidism. The plasma concentrations of testosterone (2015 ng/dL), 5 alpha-dihydrotestosterone (125 ng/dL), and androstenedione (335 ng/dL) were elevated; estradiol and estrone levels were less than 7 pg/mL. Plasma FSH and LH concentrations were more than 3 times the mean value. Plasma PRL was low; serum insulin-like growth factor I and GH-binding protein were normal. The bone age was 14 yr at a chronological age of 24 3/12 yr. Striking osteopenia was noted at the wrist. Bone mineral densitometric indexes of the lumbar spine (cancellous bone) and distal radius (cortical bone) were consistent with osteoporosis; the distal radius was -4.7 SD below the mean value for age- and sex-matched normal men; indexes of bone turnover were increased. Hyperinsulinemia, increased serum total and low density lipoprotein cholesterol, and triglycerides and decreased high density lipoprotein cholesterol were detected.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. 853 Jun 21

Classic congenital 11-beta-hydroxylase deficiency is a relatively uncommon cause of congenital adrenal hyperplasia and is characterized by virilization and often hypertension. The association of skeletal abnormalities (short metatarsal bone) and pulmonary stenosis in a patient with 11-beta-hydroxylase has been reported by our group. In this report, three new patients with congenital adrenal hyperplasia due to a defect in 11-beta-hydroxylase enzyme with short fourth metatarsals are described. Gynecomastia was noted in one patient. The relative rarity of 11-beta-hydroxylase deficiency and the association of skeletal abnormalities suggest the possibility that this is more than a mere coincidental finding.
 ...
PMID:Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency with skeletal abnormalities. 879 41