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Journal of Andrology 1991We studied the kinetics of testicular response to human chorionic gonadotropin (hCG) in oligoasthenospermic and asthenospermic patients (OAZ-AZ). The responses of...
We studied the kinetics of testicular response to human chorionic gonadotropin (hCG) in oligoasthenospermic and asthenospermic patients (OAZ-AZ). The responses of testosterone (T), androstenedione (A), 17 OH-progesterone (17OHP), and estradiol (E2) were evaluated in 60 OAZ-AZ patients and compared to those of 10 normal men. The responses of T, A, and 17OHP to hCG in the control group displayed a biphasic pattern with an initial peak at 4 hours and a second peak after 24 hours. The E2 response showed a single peak between 24 and 48 hours after hCG administration. OAZ-AZ patients had two types of T responses: group 1 (n = 40) had no first peak and group 2 (n = 20) had a normal response pattern. The response of A was similar to that of T, and the E2 response was normal in both groups. There were three types of 17OHP responses in group 1 (low, high, or normal); however, the 17OHP response was normal in group 2. Treatment of group 1 with aromatase inhibitors (aminoglutethimide or testolactone) induced an improvement of the acute T response only in patients with high or normal 17OHP response to hCG, whereas no effects were observed in patients with low 17OHP response. In group 2, the aromatase inhibitors induced no changes in the T response. These results demonstrate that in some OAZ-AZ patients (group 1, blunted T response) testicular hormone production is altered. They also suggest the presence of two enzyme blocks: one at the 17,20 desmolase level, mediated by E2, and another at early biosynthetic steps, not mediated by E2.
Topics: Adult; Aminoglutethimide; Androstenedione; Aromatase Inhibitors; Chorionic Gonadotropin; Estradiol; Humans; Infertility, Male; Male; Oligospermia; Progesterone; Radioimmunoassay; Sperm Count; Testis; Testolactone; Testosterone
PubMed: 1765563
DOI: No ID Found -
Fertility and Sterility May 1985Testicular responsiveness to a single dose of human chorionic gonadotropin was studied in five normal men before and during short-term treatment with an aromatization...
Testicular responsiveness to a single dose of human chorionic gonadotropin was studied in five normal men before and during short-term treatment with an aromatization inhibitor, testolactone (TL). TL alone resulted in significant increases in the serum concentrations of progesterone, 17-hydroxyprogesterone, 17-hydroxypregnenolone, dehydroepiandrosterone, androstenedione, and the sulfate conjugates of pregnenolone, 17-hydroxypregnenolone and testosterone (T). Concentrations of 5-androstene-3 beta, 17 beta-diol and T remained unchanged, and those of estradiol (E2) decreased. TL had no major influence on serum luteinizing hormone, follicle-stimulating hormone, prolactin, or sex-hormone-binding globulin concentrations. During TL administration, human chorionic gonadotropin stimulation led to a significantly decreased E2 response, but the T response was unchanged. Alleviation of an inhibitory influence of E2 on the steroidogenic enzymes, especially 17,20-desmolase, was probably the reason behind the increased synthesis of several T precursors. In addition, TL appeared to have an inhibitory influence on the 17 beta-reduction of T precursors. TL resulted in increased serum concentrations of some steroid sulfates, but the mechanism of this effect remains unclear.
Topics: Adult; Androgens; Chorionic Gonadotropin; Estradiol; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Sex Hormone-Binding Globulin; Testolactone; Testosterone; Time Factors
PubMed: 3922804
DOI: 10.1016/s0015-0282(16)48568-7 -
Journal of the Royal Society of Medicine Apr 1982
Topics: Adult; Breast; Breast Neoplasms; Female; Fibroma; Humans; Testolactone
PubMed: 7069698
DOI: 10.1177/014107688207500417 -
Twin Research and Human Genetics : the... Aug 2006The aim of this study was to estimate the heritability of variation in testosterone levels in 12-year-old children, and to explore the overlap in genetic and...
The aim of this study was to estimate the heritability of variation in testosterone levels in 12-year-old children, and to explore the overlap in genetic and environmental influences on circulating testosterone levels and androgen-dependent pubertal development. Midday salivary testosterone samples were collected on 2 consecutive days in a sample of 183 unselected twin pairs. Androgen-induced pubertal development was assessed using self-report Tanner scales of pubic hair development (boys and girls) and genital development (boys). A significant contribution of genetic effects to the variance in testosterone levels was found. Heritability was approximately 50% in both boys and girls. The remaining proportion of the variance in testosterone levels could be explained by nonshared environmental influences. The relatively high correlation between testosterone levels of opposite-sex dizygotic twins suggests that sex differences in genes influencing variation in testosterone levels have not yet developed in pre- and early puberty. Variance in pubertal development was explained by a large genetic component, moderate shared environmental influences, and a small nonshared environmental effect. Testosterone levels correlated moderately (r = .31) with pubertal development; the covariance between testosterone levels and pubertal development was entirely accounted for by genetic influences.
Topics: Child; Female; Genetic Variation; Humans; Longitudinal Studies; Male; Puberty; Saliva; Testolactone; Twins, Dizygotic; Twins, Monozygotic
PubMed: 16899163
DOI: 10.1375/183242706778025071 -
The International Journal of... May 2011Major questions remain about how sex hormones influence human brain development and cognition. Studies in humans and animals suggest a strong impact of androgen on the...
Major questions remain about how sex hormones influence human brain development and cognition. Studies in humans and animals suggest a strong impact of androgen on the structure and function of the medial temporal lobe (MTL) and striatum. Using voxel-based morphometry (DARTEL), we compared MTL and striatal structures in 13 [mean age (±S.D.) 12.7±3.2 yr, mean bone age 14.8±3.2 yr] boys with familial male precocious puberty (FMPP), characterized by early excess androgen secretion, and 39 healthy age-matched boys (mean age 14.3±2.5 yr). The FMPP group showed significantly larger grey-matter volume (GMV) in parahippocampal and fusiform gyri as well as putamen relative to controls. By comparison, larger GMV for controls relative to patients was only apparent in the precentral gyrus. Exploratory regression analyses that examined the impact of age on the current findings revealed a significant increase of GMV in the putamen with age in patients suffering from excess androgen but not in controls. Finally, current levels of free testosterone were obtained in the patient group. Analyses revealed a significant negative association indicating that FMPP boys with low levels of bioavailable testosterone exhibited high GMV in the bilateral striatum. The findings suggest a critical influence of androgen on human brain development and are discussed in relation to male-dominant psychiatric childhood disorders.
Topics: Adolescent; Age Factors; Androgen Antagonists; Androgens; Aromatase Inhibitors; Attention Deficit Disorder with Hyperactivity; Child; Corpus Striatum; Humans; Male; Psychiatric Status Rating Scales; Puberty, Precocious; Spironolactone; Temporal Lobe; Testolactone; Testosterone
PubMed: 20860880
DOI: 10.1017/S1461145710001136 -
Nihon Hinyokika Gakkai Zasshi. the... Feb 1991To our knowledge, the action of estradiol which is produced from testosterone by aromatase on human spermatogenesis has not been fully clarified. In oligozoospermia,...
To our knowledge, the action of estradiol which is produced from testosterone by aromatase on human spermatogenesis has not been fully clarified. In oligozoospermia, with high values of E2/T ratio, it is considered that the role of estradiol is suppressive to spermatogenesis. In this study, alteration of spermatogenesis was evaluated when serum estradiol levels were decreased by suppression of aromatase activity. Nine male infertile patients were treated with testolactone (Teslac: 1.0 g/day, for 3 months), one of the aromatase inhibitors. Four of them had an increase in sperm count (more than 10 x 10(6)/ml relative to base line). In endocrinological findings, serum estradiol levels and E2/free T ratio were significantly decreased after treatment. Serum free testosterone levels were significantly increased in all cases, presumably from decreased sex hormone binding globulin (SHBG) levels. These findings suggested the effectiveness of the administrated aromatase inhibitor. In particular four patients whose sperm counts were improved after testolactone treatment had high values of basal serum estradiol levels and E2/free T ratio before treatment, and these values were normalized after treatment. In conclusion we suggest that an aromatase inhibitor may be effective to male infertile patients with high serum estradiol levels.
Topics: Adult; Aromatase Inhibitors; Estradiol; Humans; Male; Oligospermia; Sex Hormone-Binding Globulin; Sperm Count; Testolactone; Testosterone
PubMed: 2041267
DOI: 10.5980/jpnjurol1989.82.204 -
Annals of Surgery Mar 1975A female patient with Gardner's syndrome was treated with delta1-testololactone (200 mg daily) because of growth of a large desmoid tumor in the pelvis and lower abdomen...
A female patient with Gardner's syndrome was treated with delta1-testololactone (200 mg daily) because of growth of a large desmoid tumor in the pelvis and lower abdomen and a tumor in a scar from a previous laparotomy. There was also pain and swelling of the left leg. An immediate effect of the drug therapy was complete relief of pain followed shortly thereafter by disappearance of the edema of the leg. After two months, the numerous sebaceous cysts were less prominent. The gross measurements of the diameter of the pelvic and lower abdominal tumor clearly demonstrated tumor shrinkage following therapy. Small polyps scattered over the rectal mucosa and numerous osteomata were not demonstrably affected. After one year of treatment with delta1-testololactone, a laparotomy for partial small bowel obstruction was necessary. Obstruction was caused by the involvement of small bowel mesentery and the bowel itself in a contracted residuum of dense fibrous tissue. Substitution of theophylline and chlorothiazide for the testololactone in Januray 1974 was followed by further diminution of the measurable abdominal and pelvic desmoids. All of these compounds synergize the action of 3',5'-adenosine monophosphate and at least the latter two may function by inhibiting the action of 3',5'-adenosine monophosphate diesterase.
Topics: Abdominal Muscles; Abdominal Neoplasms; Adult; Bone Neoplasms; Cyclic AMP; Female; Fibroma; Humans; Intestinal Polyps; Neoplasms, Multiple Primary; Odontogenic Tumors; Osteoma; Pelvic Neoplasms; Phosphodiesterase Inhibitors; Skin Neoplasms; Syndrome; Testolactone; Time Factors
PubMed: 165790
DOI: 10.1097/00000658-197503000-00009 -
Proceedings of the National Academy of... Mar 1987This report describes the induction of cell-type-specific maturation, by dibutyryl-cAMP and testololactone, of neuronal and glial properties in a family of cell lines...
This report describes the induction of cell-type-specific maturation, by dibutyryl-cAMP and testololactone, of neuronal and glial properties in a family of cell lines derived from a rat peripheral neurotumor, RT4. This maturation allows further understanding of the process of determination because of the close lineage relationship between the cell types of the RT4 family. The RT4 family is characterized by the spontaneous conversion of one of the cell types, RT4-AC (stem-cell type), to any of three derivative cell types, RT4-B, RT4-D, or RT4-E, with a frequency of about 10(-5). The RT4-AC cells express some properties characteristic of both neuronal and glial cells. Of these neural properties expressed by RT4-AC cells, only the neuronal properties are expressed by the RT4-B and RT4-E cells, and only the glial properties are expressed by the RT4-D cells. This in vitro cell-type conversion of RT4-AC to three derivative cell types is a branch point for the coordinate regulation of several properties and seems to resemble determination in vivo. In our standard culture conditions, several other neuronal and glial properties are not expressed by these cell types. However, addition of dibutyryl-cAMP induces expression of additional properties, in a cell-type-specific manner: formation of long cellular processes in the RT4-B8 and RT4-E5 cell lines and expression of high-affinity uptake of gamma-aminobutyric acid, by a glial-cell-specific mechanism, in the RT4-D6-2 cell line. These new properties are maximally expressed 2-3 days after addition of dibutyryl-cAMP. This indicates that conversion of RT4-AC to the derivative cell types is also a branch point for the regulation of cell-type-specific properties whose expression is responsive to cAMP. Thus, the potential for maturation in response to increased cAMP is a property that segregates in a cell-type-specific manner and is activated at the determinational level in this system.
Topics: Autoradiography; Bucladesine; Cell Line; Kinetics; Neurons; Testolactone; Tritium; gamma-Aminobutyric Acid
PubMed: 3029777
DOI: 10.1073/pnas.84.5.1309 -
Journal of Medicinal Chemistry Oct 2005Inhibition of aromatase is an efficient approach for the prevention and treatment of breast cancer. New A,D-ring modified steroid analogues of formestane and...
Inhibition of aromatase is an efficient approach for the prevention and treatment of breast cancer. New A,D-ring modified steroid analogues of formestane and testolactone were designed and synthesized and their biochemical activity was investigated in vitro in an attempt to find new aromatase inhibitors and to gain insight into their structure-activity relationships (SAR). All compounds tested were less active than formestane. However, the 3-deoxy steroidal olefin 3a and its epoxide derivative 4a proved to be strong competitive aromatase inhibitors (K(i) = 50 and 38 nM and IC50 = 225 and 145 nM, respectively). According to our findings, the C-3 carbonyl group is not essential for anti-aromatase activity, but 5alpha-stereochemistry and some planarity in the steroidal framework is required. Furthermore, modification of the steroidal cyclopentanone D-ring, by construction of a delta-lactone six-membered ring, decreases the inhibitory potency. From the results obtained, it may be concluded that the binding pocket of the active site of aromatase requires planarity in the region of the steroid A,B-rings and the D-ring structure is critical for the binding.
Topics: Androstanes; Androstenedione; Aromatase Inhibitors; Cyclopentanes; Drug Design; Humans; In Vitro Techniques; Lactones; Microsomes; Placenta; Stereoisomerism; Structure-Activity Relationship
PubMed: 16190763
DOI: 10.1021/jm050129p -
Journal of Pharmaceutical Analysis Feb 2012A fast screening protocol was developed for the simultaneous determination of nine anti-estrogenic agents (aminoglutethimide, anastrozole, clomiphene, drostanolone,...
A fast screening protocol was developed for the simultaneous determination of nine anti-estrogenic agents (aminoglutethimide, anastrozole, clomiphene, drostanolone, formestane, letrozole, mesterolone, tamoxifen, testolactone) plus five of their metabolites in human urine. After an enzymatic hydrolysis, these compounds can be extracted simultaneously from urine with a simple liquid-liquid extraction at alkaline conditions. The analytes were subsequently analyzed by fast-gas chromatography/mass spectrometry (fast-GC/MS) after derivatization. The use of a short column, high-flow carrier gas velocity and fast temperature ramping produced an efficient separation of all analytes in about 4 min, allowing a processing rate of 10 samples/h. The present analytical method was validated according to UNI EN ISO/IEC 17025 guidelines for qualitative methods. The range of investigated parameters included the limit of detection, selectivity, linearity, repeatability, robustness and extraction efficiency. High MS-sampling rate, using a benchtop quadrupole mass analyzer, resulted in accurate peak shape definition under both scan and selected ion monitoring modes, and high sensitivity in the latter mode. Therefore, the performances of the method are comparable to the ones obtainable from traditional GC/MS analysis. The method was successfully tested on real samples arising from clinical treatments of hospitalized patients and could profitably be used for clinical studies on anti-estrogenic drug administration.
PubMed: 29403714
DOI: 10.1016/j.jpha.2011.09.011