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)

Pituitary content or concentration of follicle-stimulating hormone (FSH), prolactin and growth hormone in the genetically androgen insensitive male rat pseudohermaphrodite is intermediate between normal male and female rats, while pituitary luteinizing hormone (LH) concentration and serum FSH levels are the same as in the normal male. The concentration of serum LH, prolactin and growth hormone indicated no sexual dimorphism. Although the pseudohermaphrodite is genetically male with a female phenotype, our results suggest some degree of masculinization of the hypothalamic-pituitary system.
 ...
PMID:Pituitary hormone secretion in the genectically male rat pseudohermaphrodite. 111 35

The physiologic activity of ethylmorphine demethylase (EMDM) is 2.5 times greater in adult male rats than in females. Defeminization, effected neonatally by testicular androgens, causes 65% of the increase while masculinization causes the rest. Castration of the intact adult does not alter the defeminized activity of the enzyme but abolishes its masculinized activity. Testosterone restores the latter. Adults that are not defeminized, because of neonatal castration, have enzymes unresponsive to testosterone. Thus, defeminization seems necessary for the expression of masculine activity. This was studied by castrating males at birth (day 1) and implanting capsules of testosterone propionate on day 35. On day 71, the activity had increased 4.4-fold to physiologic levels, compared with rats receiving no steroid (1.9 nmol.min-1.mg-1). Removal of the implant on day 71 decreased the activity on day 84 to that of the no-steroid rats. Thus, defeminization is neither caused by androgen in peripubertal rats nor needed to effect full physiologic activity of the enzyme. The activation of EMDM by peripubertal testosterone may reflect its regulation of growth hormone; first, testosterone (days 35-71) failed to increase enzyme activity in males hypophysectomized on day 35; second, growth hormone infused (5 micrograms.h-1) over days 71-76 blocked the activation, actually decreasing activity 3.7-fold; third, the activity induced by testosterone was further increased (26%) by growth hormone release-inhibiting hormone (5 micrograms.h-1, days 71-76).
 ...
PMID:The effects of peripubertal testosterone on ethylmorphine demethylase activity in adult rats testectomized neonatally. 205 8

The hormonal regulation of the sexually differentiated cytochrome P-450 isozyme which catalyzes 16 alpha-hydroxylation of testosterone and 4-androstene-3,17-dione in male rat liver (P-450(16) alpha) was investigated. Estradiol valerate injection of male rats caused a decrease in P-450(16) alpha levels to almost the female level, while methyltrienolone injection had the reverse effect in female animals. Hypophysectomy abolished the sex difference in P-450(16) alpha levels. Human growth hormone infusion into male rats, mimicking the female pattern of growth hormone secretion, caused a feminization of P-450(16) alpha levels. The same effect was also seen in hypophysectomized rats of both sexes. In contrast, a different administration schedule involving 12 h injections of human growth hormone, mimicking the male pattern of growth hormone secretion, caused a masculinization of P-450(16) alpha levels in hypophysectomized rats, at a daily dose which causes feminization when given by infusion. Thus, the level of expression of P-450(16) alpha in the liver is dependent on the temporal pattern of blood growth hormone levels. While infusion of rat growth hormone into male rats also feminized the P-450(16) alpha levels, infusion of ovine prolactin had no effect. Ontogenic studies showed that the developmental pattern of P-450(16) alpha expression in the liver coincided with the known pattern of development of the sexual differentiation of hepatic steroid 16 alpha-hydroxylase activity and of the diurnal pattern of growth hormone secretion.
 ...
PMID:Hormonal and developmental regulation of expression of the hepatic microsomal steroid 16 alpha-hydroxylase cytochrome P-450 apoprotein in the rat. 387 34

Clinical and endocrine features of a patient with ovarian hyperthecosis and a growth hormone-secreting pituitary tumor are reported. A 36-year-old nulliparous woman had a history of severe hirsutism and virilization of long duration. Ovarian catheterization studies at surgery confirmed an ovarian source of excessive androgen production. Ovarian pathology revealed stromal hyperthecosis. Growth hormone levels were elevated and could not be suppressed with glucose ingestion; a pneumoencephalogram revealed the presence of a pituitary tumor. The possible cause-and-effect relationship of these 2 relatively uncommon disorders is discussed.
 ...
PMID:Hyperthecosis of the ovaries in acromegaly. 739 21

Current therapeutic approaches to postmenopausal bone loss or established osteoporosis vary widely among the different regions of the world. Because no treatment of osteoporosis has unequivocally demonstrated full prevention of the appearance or the recurrence of axial or peripheral fractures so far, many investigational compounds are being developed. Anabolic steroids act mainly as inhibitors of bone resorption with very few, if any, effects on bone formation. Because of the high occurrence of signs of virilization and the weak effects on bone structure, the risk/benefit ratio in osteoporosis should be considered at least problematic. If ongoing large-scale trials confirm the expected benefits of estrogen antagonist/agonists on the skeleton and confirm no cardiovascular risk to postmenopausal women with optimal uterine safety, these substances are likely to become the most prominent alternative to hormonal replacement therapy after the menopause. Additional studies are requested to evaluate the potential benefit of growth hormone or insulin-like growth factors in treatment of osteoporosis. Ipriflavone acts predominantly as an inhibitor of bone resorption. To confirm the efficacy of ipriflavone on the prevention of vertebral fractures and its effects on bone mineral density in women with postmenopausal established osteoporosis, a large multicentric European study is being conducted. Treatment with parathyroid peptides induces a significant gain in bone mass, mainly in the axial skeleton. Long-term studies that compare peptides, doses, and regimes are needed to better understand the exact position of parathyroid peptides as treatment of osteoporosis. Prolonged administration of strontium to postmenopausal osteoporotic women resulted in a decoupling between bone resorption and formation that yielded a significant increase in the lumbar spine bone mineral density of treated subjects. In the view of these promising results and of the excellent tolerance of strontium during preliminary trials, additional investigations of this compound in prevention and treatment of osteoporosis should be promptly initiated. Several other compounds have been punctually suggested for treatment of osteoporosis or are at very early stages of development. Finally, besides pharmacologic approaches to the treatment of osteoporosis, hip fractures may also be reduced by the use of hip protectors.
 ...
PMID:Miscellaneous and experimental agents. 900 Nov 64

A striking sex-related difference in postpubertal growth and growth hormone (GH) secretory pattern in the rat has been described. Although this sexual dimorphism seems to be determined by the neonatal effects of gonadal steroids on the hypothalamus, peripubertal exposure to steroids also plays an important role. In order to study the real influence of the hypothalamic sex and/or peripubertal gonadal steroids, the growth pattern of female and male rats in response to neonatal and peripubertal sexual steroid treatments was studied using microknemometry, a technique that allows non-invasive daily measurements of rat tibial growth rate. Neonatal steroid environment in males was modified by castration on day 1, whereas in females it was changed by a single neonatal testosterone administration on day 5 followed by castration at 13 days of age. From the onset of puberty to adulthood, both female and male animals received testosterone or estrogens, respectively. Neonatal treatment alone, i.e. androgenization of female and castration of male rats, were only able to induce a partial reversal of the original sex-dependent growth pattern. Additional peripubertal treatments achieved a complete change in the sex-linked growth pattern. Consistent with the effects observed on growth, the pituitary GH concentration was significantly increased in females, and diminished in males, when they were treated both at the neonatal and peripubertal stages. However, only this latter group, whose growth was more seriously compromised, showed decreased plasma insulin-like growth factor-I (IGF-I) levels. In conclusion, a complete feminization of male tibial growth pattern or masculinization of female pattern can only be achieved by maintaining the new steroid environment from puberty to adulthood.
 ...
PMID:Daily rat tibial growth in vivo following hypothalamic sex reversal with neonatal and pubertal treatments with gonadal steroids. 1120 30

A role for 5alpha-reduction in androgen physiology was first established with the recognition that dihydrotestosterone, the 5alpha-reduced metabolite of testosterone, is formed in many androgen target tissues, binds to the androgen receptor with greater affinity than testosterone, and plays an essential role in virilization of the urogenital sinus and urogenital tubercle during male development. Two 5alpha-reductases perform this reaction, and both isoenzymes utilize NADPH as cofactor and have broad specificity for steroids containing a delta4,3-keto configuration. 5alpha-Reduction, which is essentially irreversible, flattens the steroid molecule because of altered relation of the A and B rings, and stabilizes the hormone-receptor complex. Studies involving in vitro reporter gene assays and intact mice in which both isoenzymes are disrupted, indicate that the fundamental effect of dihydrotestosterone formation is to amplify hormonal signals that can be mediated by testosterone at higher concentrations. 5alpha-Reduction also plays a role in the action of other steroid hormones, including the plant growth hormone, brassinolide, the boar pheromones, androstanol and androstenol, progesterone (in some species), and, possibly, aldosterone and cortisol. The fact that the reaction is important in plants and animals implies a fundamental role in steroid hormone action.
 ...
PMID:The role of 5alpha-reduction in steroid hormone physiology. 1199 20

A girl aged 5 years and 6 months presented with premature thelarche in our outpatient clinic. During long-term observation, we recorded growth acceleration, advanced bone age, and elevated oestradiol levels which together were taken to confirm the diagnosis of precocious puberty. The patient was successfully treated with a gonadotropin-releasing hormone agonist, but in view of the poor growth prognosis, recombinant human growth hormone was administered concurrently. At the age of 9 years and 6 months a mild clitoris enlargement and conspicuous muscle development without any further signs of virilization were noticed. Laboratory findings showed high values for testosterone and normal basal values for 17-hydroxyprogesterone and dehydroepinadrosterone sulphate. Explorative laparotomy revealed a gonadoblastoma arising from testicular structures on the left, a female streak gonad on the right side, and normal uterus and fallopian tubes. The karyotype was 46,XY/45,X. These findings confirmed the diagnosis of mixed gonadal dysgenesis with testosterone-producing gonadoblastoma.
 ...
PMID:Mixed gonadal dysgenesis and precocious puberty. 1216 78

Growth is disturbed by adrenal hypersecretion of androgens or cortisol. Androgen excess in virilizing adrenal tumours causes advanced growth and bone age. In 9 girls with virilizing tumours, mean heights at diagnosis and final heights were 1.23 +/- 0.42 and 1.3 +/- 0.37 SDS respectively. In poorly controlled CAH, excess androgens cause early epiphyseal fusion and adult short stature. Increased growth occurs only after 18 months of age, even in untreated CAH, i.e. hydrocortisone >10 mg/m(2)/day is not generally required and may suppress infantile growth, affecting childhood and adult height. Growth was studied in 19 patients, aged 6.4-17.8 years, with Cushing's disease (CD). At diagnosis, mean height SDS was -1.81 (1.2 to -4.17), 53% < -1.8 SDS, height velocity in 6 was 0.9-3.8 cm/year and mean BMI SDS 2.29 (0.7-5.06). From 1983 to 2001, CD was cured in 18 patients (61%) by transsphenoidal surgery (TSS) alone and 39% by TSS plus pituitary irradiation (RT). In 13 patients, growth hormone (GH) was assessed by ITT/glucagons at 1-108 months after cure. Four had severe GH deficiency (<9 mU/l), 7 subnormal (10-29 mU/l) and 2 normal (>30 mU/l) GH status. Subnormal GH was present in 7 subjects >2 years after TSS or RT cure. In 10 subjects, aged 12.9 +/- 3.4 years, growth after cure was studied for 9.1 +/- 5.0 years. Nine had no catch-up growth in the interval of 0.3-1.1 years after cure (mean HV 5.3 +/- 2.4 cm/year). All these had GH deficiency peak GH 0.5-20.9 mU/l, and received hGH 2.7 mg/m(2)/week, 3 with GnRHa. All 10 showed long-term catch-up growth with mean delta SDS at diagnosis (Ht SDS-target Ht SDS) -1.72 +/- 1.26 improving to -0.83 +/- 1.08 (p = 0.0005) at latest of final Ht. At diagnosis, virilization was present in 82% of 17 patients with CD. Mean SDS values of serum androstenedione, DHEA-S and testosterone were normal, i.e. 0.72 (-2.9 to 3.0), -0.8 (6.0 to 2.2), 0.7 (-7.9 to 9.5) respectively, whereas SHBG was reduced at -2.1 (-5.3 to 1.2), increasing free androgen levels. Bone age (BA) was delayed (mean 1.46 years) in 14/16 patients, suggesting cortisol excess contributed more then androgen effect to skeletal maturation. In conclusion, most paediatric patients with CD had subnormal linear growth with delayed BA. After cure by TSS or pituitary irradiation, GH deficiency was frequent and persisted for many years. Treatment with hGH induced significant long-term catch-up growth leading to reasonable final height.
 ...
PMID:Growth in disorders of adrenal hyperfunction. 1237 13

Thyroid hormone deficiency affects all tissues of the body, including multiple endocrine changes that alter growth hormone, corticotrophin, glucocorticoids, and gonadal function. Primary hypothyroidism is associated with hypogonadotropic hypogonadism, which is reversible with thyroid hormone replacement therapy. In male children follicle-stimulating hormone (FSH) is elevated and associated with testicular enlargement without virilization. Men with primary hypothyroidism have subnormal responses of luteinizing hormone (LH) to gonadotropin-releasing hormone (GnRH) administration and normal response to human chorionic gonadotropin (hCG). Free testosterone concentrations are reduced in men with primary hypothyroidism and thyroid hormone replacement normalizes free testosterone concentrations. In men with primary hypothyroidism, prolactin is not consistently elevated (except in men and children with longstanding severe primary hypothyroidism), but prolactin declines following thyroid hormone replacement therapy. Thyroid hormone is known to affect sex hormone-binding hormonal globulin (SHBG) concentrations. Men with hyperthyroidism have elevated concentrations of testosterone and SHBG. Thyroid hormone therapy in normal men may also duplicate this elevation. In addition estradiol elevations are observed in men with hyperthyroidism, and gynecomastia is common in them as well. In contrast to patients with primary hypothyroidism, men with hyperthyroidism exhibit hyperresponsiveness of LH to GnRH administration and subnormal responses to hCG. Radioactive iodine therapy (RAI) of men treated for thyroid cancer produces a dose-dependent impairment of spermatogenesis and elevation of FSH up to approximately 2 years. Permanent testicular germ cell damage may occur in men treated with high doses of RAI. RAI commonly increases serum concentrations of FSH and LH while reducing inhibin B levels without affecting serum concentrations of testosterone. Thus, radioiodine therapy transiently impairs both germinal and Leydig cell function that usually recover by 18 months posttherapy.
 ...
PMID:The interrelationships between thyroid dysfunction and hypogonadism in men and boys. 1514 73


1 2 3 Next >>