Defective androgen action at the cellular level in the androgen resistance syndromes. I. Differences between the complete and incomplete testicular feminization syndromes.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Medina.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The role of oestrogens on gonadotrophin secretion was assessed in three related patients with the complete form of testicular feminization syndrome. Serum LH and FSH levels were measured before and after LRH stimulation as well as before, during and after chronic clomiphene citrate administration. Moderately elevated LH basal levels with a significant LH rise following LRH were observed. Normal or even low FSH level with poor response to LRH were found in all subjects. Administration of clomiphene citrate resulted in a significant serum LH increase without any change of FSH. Following castration both LH and FSH rose and a normal response to LRH was observed. These results were interpreted as demonstrating that, while endogenous oestrogens modulate LH secretion in patients with androgen unresponsiveness, it plays no role in regulating FSH secretion and suggested that a factor of testicular origin without androgenic or oestrogenic activity is responsible for FSH regulation.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Four postpubertal 46 XY male patients with an inherited form of bilateral gynecomastia were studied to delineate the nature of the disease. Normal serum FSH and moderately elevated serum LH with concomitantly increased circulating levels of testosterone (T) and estradiol (E2) were found persistently in all cases in blood samples drawn at frequent intervals. LRH pituitary stimulation resulted in an exaggerated LH response and a normal FSH response. Chronic administration of T-cyclopentylate failed to decrease serum LH levels. The peripheral conversion rate of androstenedione to estrone was within normal limits. All patients had low ejaculate volumes with relatively normal spermatozoa counts. Testicular biopsies revealed normal Leydig cells and complete spermatogenesis. Urological examination disclosed that the prostate gland was extremely small. The breast tissue demonstrated the presence of tubular structures as well as the specific binding of [3H]T and [3H]dihydrotestosterone (DHT), which was inhibited by nonlabeled T, DHT, E2, and progesterone, but not by cortisol. The pedigree suggested a recessive X-linked inherited trait. A patient with a nonfamilial form of gynecomastia served as a control in all studies. These data were interpreted as demonstrating that this inherited type of gynecomastia represents the mildest expression of the androgen resistance syndromes and, therefore, belongs to the type 1 form of familial incomplete male pseudohermaphroditism.
The neuroendocrine function of a 19 years old female dwarf with primary amenorrhoea and lack of sexual development (asexual ateleiosis) was studied. Undetectable fasting plasma levels of growth hormone (GH) and a lack of response to three different provocative stimuli was observed. Oestrogen administratin did not modify the GH response. Thyroid and adrenal function were within normal limits. Undetectable plasma levels of immunoreactive oestradiol and lack of oestrogenic activity in vaginal smears indicated absence of ovarian function. Low levels of circulating gonadotrophins with a significant rise after synthetic LH-RH administration was demonstrated, while clomiphene citrate failed to induce ovulation. Following 6 months of continuous GH administration a significant increase in the growth rate was evident, whereas no pubertal development was observed. These data are interpreted as demonstrating the suprahypophyseal origin of the sexual infantilism in a patient with inappropriate GH secretion. It is suggested that a combined deficiency of LH-RH and GH-RH may account for the aetiology of this disorder.
The nerve growth factor is a polypeptide isolated from the salivary glands of certain laboratory animals. Its greatest physiological effect is on the autonomic nervous system. When antiserum against this nerve growth factor was injected in newborn animals nearly total destruction of the sympathetic ganglia was noted, a procedure known as immunosympathectomy. The anti-nerve growth factor labeled with 131iodine was injected in rats to determine organ distribution at different intervals (2, 4, 6, 8 and 24 hours). A selective concentration was obtained in the sympathetic ganglia and adrenal medulla (adrenal ganglia) 4 hours after the intravenous injection of 50 muCi. 131Iodine anti-nerve growth factor, with a specific activity of 0.001 gm. per mCi., permitted scanning of this structure for the first time. No intolerance or radiotoxicity has been observed in the animals and the results are encouraging. Radioimmunoscanning of the sympathetic ganglia and adrenal medulla in the human and radioimmunosympathectomy of the structures are being studied currently and will be subjects of future communications.
Explore the source record for details and available documents.
Four 46,XY siblings with congenital bilateral megalorchidia, marcogenitosomia, and severe mental deficiency were investigated. The testicular size was significantly larger than age-matched normal males. A normal hypothalamic-pituitary gonadotropin function was demonstrated by the finding of normal levels of luteinizing and follicle-stimulating hormones in blood samples drawn at frequent intervals and by normal responses to gonadotropin-releasing hormone and testosterone administration. A normal testicular function was shown by the finding of normal (a) plasma testosterone and estradiol levels, (b) gonadal response to human chorionic gonadotropin, (c) sperm analysis, and (d) morphology and cell architecture of the testes. Adrenal function was found to be within normal limits. These results demonstrated the existence of normofunctional testicular hyperplasia. The family studies suggested that this distinct congenital disorders is inherited as an X-linked recessive trait.
The circulating levels of of radioimmunoassayable LH and FSH in three postmenopausal women were measured in samples drawn at one minute intervals for a period of 150 or 300 min in order to ascertain the existance of short term oscillation on the plasma content of pituitary gonadotropins. Radioimmunoassay methods and sampling procedures fulfilled all the requirements of quality control. Rapid and non-coincident oscillation in the plasma levels of both LH and FSH at the interval studied were observed in all cases. Statistical analysis disclosed that in addition to short-term gonadotropin fluctuation, the data successfully fit in a 120 min periodic function and the graph resembled a sine wave that was also compatible with an ultradian oscillatory pattern.
The plasma concentrations and episodic fluctuations of immunoreactive FSH and LH as well as the pituitary sensitivity to LH-RH stimulation were evaluated in post-menopausal women. The subjects were divided into 4 groups according to age. Group 1: 60-70 years old (n = 11), group 2: 70-80 years old (n = 22), group 3: 80-90 years old (n = 31) and group 4: 90-100 years old (n = 8). Standards used in gonadotrophin radioimmuno-assays included the LER-907 preparation and a pooled post-menopausal serum. Since it was found that circulating gonadotrophins have an immunological pattern different from that shown by the pituitary preparation, the results were expressed in mIU/ml calculated accordingly to the immunological behavior of pooled post-menopausal sera. The mean (+/- SE) plasma levels of FSH (mIU/ml) were: group ): 105 +/- 9.5, group 2: 149.3 +/- 10.5, group 3: 124.8 +/- 7.1 and group 4: 149.4 +/- 25.3. The mean (+/- SE) plasma levels of LH (mIU/ml) were: group 1: 81.9 +/- 12.5, group 2: 95.4 +/- 9.9, group 3: 84.3 +/- 7.7 and group 4: 113.5 +/- 19.1. No statistically significant differences were observed among the 4 groups. One patient from each group was randomly selected in order to evaluate their LH and FSH episodic release as well as their pituitary responsiveness to exogenous stimulation. A pulsatile plasma pattern of gonadotrophin and a normal pituitary response to LH-RH injection were observed in the 4 patients studied. The results are interpreted as demonstrating that normal pituitary gonadotrophin function and pituitary reserve and responsiveness to exogenous stimulation are maintained in women of advanced age.
Hypothalamic and pituitary gonadotropin function and responsiveness in four patients with well-documented Stein-Leventhal syndrome were studied. All patients were of reproductive age and had had menstrual disorders since menarche. Estrogen production was assessed by measuring the circulating levels of immunoreactive estradiol, by vaginal smears, and by the progestogen-induced menses test. Gonadotropin function was evaluated by measuring the serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in blood samples obtained at 15-minute intervals for 150 minutes. Pituitary gonadotropin reserve and responsiveness were studied by giving an intravenous bolus of synthetic LH-releasing hormone (LH-RH) and measuring the circulating gonadotropin levels before and after the injection.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.