TESTOSTERONE 5α-REDUCTION IN THE SKIN OF NORMAL SUBJECTS AND OF PATIENTS WITH ABNORMAL SEX DEVELOPMENT

1975 ◽  
Vol 79 (1) ◽  
pp. 164-176 ◽  
Author(s):  
Frédérique Kuttenn ◽  
Pierre Mauvais-Jarvis
Keyword(s):  
Conversion Rate ◽  
Reductase Activity ◽  
Human Subjects ◽  
Sex Differentiation ◽  
Normal Subjects ◽  
Normal Male ◽  
Skin Sample ◽  
Reduction Activity ◽  
Sex Development ◽  
Normal Men

ABSTRACT Human pubic skin was obtained from normal subjects and patients with abnormal sex differentiation. Skin samples (200 mg) supplemented with NADPH, were incubated for 1 h with labelled testosterone. The conversion of testosterone to dihydrotestosterone1), 3α- and 3β-androstanediol was calculated. This conversion averaged 14.9 ± 3.4 % (se) in 11 normal men and 3.6 ± 1.4 % (se) in 8 normal women. In 4 children as in 4 young hypogonadotrophic hypogonadal men, the conversion rate of testosterone to 5α-reduced metabolites was low (0.8 to 3.5%) and increased at puberty (13.5 to 19.2%). After administration of HCG for 3 months to 1 of the hypogonadal men, it reached 30.2 %. Inversely, the formation of dihydrotestosterone and androstanediols from testosterone was suppressed in 2 men treated with large doses of oestrogen. In 3 subjects with an incomplete form of testicular feminization syndrome, the conversion rate of testosterone to 5α-reduced metabolites was in the normal male range (6.4 to 18.3%), whereas it was low in one case of the complete form of the syndrome (1.5%). In 9 women with idiopathic hirsutism the rate of 5α-reduced metabolites recovered from testosterone was close to that of normal men (13.5 ± 5.5% (se). From theseresults, it is postulated that in human subjects, there is a good correlation between hair growth in skin from a sexual area and the extent of testosterone 5α-reduction in this tissue. Such an enzymatic activity might be induced by active androgens; this latter hypothesis is in good agreement with the increase of 5α-reduction activity observed at puberty or after treatment of young hypogonadal males. In addition, it is pointed out that a positive correlation is observed between the 5α-reductase activity present in each skin sample studied and the urinary 3α-androstanediol found for the same individual. This confirms our previous findings suggesting that the determination of urinary 3α-androstanediol might prove of clinical interest in the evaluation of the androgenic status in human subjects.

PLASMA CONCENTRATION OF TESTOSTERONE, DIHYDROTESTOSTERONE, TESTOSTERONE-OESTRADIOL BINDING GLOBULIN, AND PITUITARY GONADOTROPHINS IN THE SYNDROME OF MALE PSEUDO-HERMAPHRODITISM WITH TESTICULAR FEMINIZATION

1972 ◽  
Vol 70 (2) ◽  
pp. 331-341 ◽  
Author(s):  
Roland R. Tremblay ◽  
Thomas P. Foley ◽  
Pierre Corvol ◽  
In-Joo Park ◽  
Avinoam Kowarski ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Reductase Activity ◽  
Venous Blood ◽  
Follicle Stimulating Hormone ◽  
Normal Subjects ◽  
Normal Male ◽  
Testicular Feminization ◽  
Peripheral Plasma ◽  
Serum Lh ◽  
High Concentrations

ABSTRACT Twenty patients with the syndrome of testicular feminization have been studied along with a group of normal subjects of both sexes and of comparable ages. Peripheral and gonadal venous blood were analysed for their content in testosterone (T), androstenedione (Δ), dihydrotestosterone (DHT), testosterone-oestradiol binding globulin (TeBG), luteinizing hormone (LH) and follicle stimulating hormone (FSH). Normal or even higher than normal male concentrations of T, Δ, and DHT were observed. An actual secretion of the three androgens by the testis was demonstrated. Elevated levels of serum LH were found despite normal male or higher levels of T, Δ, and DHT. High concentrations of TeBG presumably could alter the dynamics of plasma androgens. The gonadal production of DHT and the normal levels of DHT in peripheral plasma shows that 5α-reductase activity is definitely present in the patients.

scholarly journals The metabolism of14C-labelled α-methyldopa in normal and hypertensive human subjects

1972 ◽  
Vol 129 (1) ◽  
pp. 1-10 ◽  
Author(s):  
W. Y. W. Au ◽  
L. G. Dring ◽  
D. G. Grahame-Smith ◽  
P. Isaac ◽  
R. T. Williams
Keyword(s):  
Human Subjects ◽  
Normal Subjects ◽  
Main Metabolite ◽  
Hypertensive Patients ◽  
The One ◽  
Normal Men

1. The fate of orally administered14C-labelled l-α-methyldopa has been examined in three normal men and in eight hypertensive patients who responded to the drug and three who did not. 2. The output of14C in the urine in 2 days and in the faeces in 4 days was not very different in any of the subjects. The normals excreted about 40% of the dose in the urine and 60% in the faeces, the responders 52% (range 35–60%) and 45% and the non-responders 42% and 41%. Most of the urinary14C radioactivity was eliminated in 24h after dosing. 3. The main metabolite in the urine was free and conjugated α-methyldopa (normal men, 23% responders, 37% non-responders, 25% of the dose). Free and conjugated 3-O-methyl-α-methyldopa was about 4% in all subjects, total amines (α-methyldopamine and 3-O-methyl-α-methyldopamine) about 6% and ketones (mainly 3,4-dihydroxyphenylacetone) about 3%. 4. The output of α-methyldopamine (2–4% of dose), 3-O-methyl-α-methyldopamine (0.3%) and 3,4-dihydroxyphenylacetone (3–5%) was similar in the one normal and two responders examined. 5. The faecal14C in all subjects was unchanged l-α-methyldopa. 6. In general, the amounts of the metabolites in the urine in normal men and in responding and non-responding patients were quantitatively similar, except in one non-responding patient who converted nearly two-thirds of the absorbed drug into amines and ketones. There appeared to be no correlation between metabolites in the urine and response or lack of response to the drug. 7. In two normal subjects 70–80% of d-α-methyldopa was excreted unchanged in the faeces. Of the absorbed compound most (9–14% of the dose) was excreted as the free and conjugated drug together with a small amount (1–2%) of 3-O-methyl-α-methyldopa. No amines and only traces of ketone were excreted.

scholarly journals THE SYNTHESIS, STORAGE, AND EXCRETION OF CREATINE, CREATININE, AND GLYCOCYAMINE IN PROGRESSIVE MUSCULAR DYSTROPHY AND THE EFFECTS OF CERTAIN HORMONES ON THESE PROCESSES

1945 ◽  
Vol 81 (5) ◽  
pp. 423-438 ◽  
Author(s):  
Charles L. Hoagland ◽  
Helena Gilder ◽  
Robert E. Shank
Keyword(s):  
Muscular Dystrophy ◽  
Testosterone Propionate ◽  
Human Subjects ◽  
Normal Subjects ◽  
Muscle Disease ◽  
Normal Male ◽  
Methyl Groups ◽  
Progressive Muscular Dystrophy ◽  
Urinary Creatinine ◽  
Desoxycorticosterone Acetate

The diminished excretion of creatinine in progressive muscular dystrophy is a more striking and specific phenomenon than the excess excretion of creatine, marked though this is. While creatinuria is invariably encountered in all cases of long-standing dystrophy, the extent to which the excretion of creatinine is decreased provides a more reliable indication of the severity of the disease since an excess output of creatine may occur physiologically in normal human subjects and in many pathological conditions not known to be associated with muscle disease. In progressive muscular dystrophy the residual muscle mass, as inferred from the excretion of creatinine, provides a useful index of the state of the disease at any given time. Although there is excessive creatinuria in progressive muscular dystrophy, there is no evidence that a deprivation of methyl stores occurs through a loss of urinary creatine. The loss of methyl groups contained in the excess creatine is, under ordinary conditions of diet, almost exactly compensated for by a drop in the excretion of methyl groups in the urinary creatinine. Testosterone propionate, administered over variable periods of time, resulted in the retention of creatine both in normal male children and in male children with progressive muscular dystrophy, as shown in the normal subjects by a diminution in creatine output, and in both by an excess creatinuria for variable periods of time following withdrawal of the hormone. An increase in the excretion of creatine in progressive muscular dystrophy occurred following the administration of methyl testosterone. Neither testosterone propionate nor methyl testosterone appeared to effect any consistent change in the output or urinary creatinine. No effects on the excretion of creatine and creatinine were observed following the prolonged administration of concentrate of gonadotropic and thyrotropic principles of the hypophysis, or from the administration of desoxycorticosterone acetate to patients with progressive muscular dystrophy. Except in one case, in which marked improvement was observed following the administration of testosterone propionate, no effects on the clinical course of the patients with progressive muscular dystrophy were observed as a result of treatment by any of the various hormones employed in this study.

scholarly journals Intragenic Duplication of DMRT1 in a SRY-Negative Boy with 46,XX Disorder of Sex Development

2021 ◽  
Author(s):  
Veronica Bertini ◽  
Fulvia Baldinotti ◽  
Nina Tyutyusheva ◽  
Camillo Rosano ◽  
Cinzia Cosini ◽  
...  
Keyword(s):  
De Novo ◽  
Sex Differentiation ◽  
Disorders Of Sex Development ◽  
Comparative Genomic ◽  
Normal Male ◽  
Testicular Development ◽  
Targeted Next Generation Sequencing ◽  
Sex Development ◽  
Intragenic Duplication ◽  
Xx Males

Background. 46,XX disorders of sex development are rare. Approximately, 90% of XX males are SRY-positive, while testicular development in the absence of SRY takes place in a minority. Methods: A boy with 46,XX karyotype (SRY-negative; absence of SOX9 duplications) was investigated by targeted Next Generation Sequencing (NGS), Multiplex ligation-dependent probe amplification (MLPA), and Comparative Genomic Hybridization array (CGH-array). Results: The boy had normal male phenotype and normal prepubertal values of testicular hormones. He presented a heterozygous duplication of 49.626 bp, encompassing exons 2 and 3 of DMRT1. The result was arr[GRCh37] 9p24.3(845893_895518)x3. Since both breakpoints are harbored in the intronic regions, the duplication does not stop or shift the coding frame. Additional known pathogenic or uncertain variants in pro-testis gene cascade were not identified. Conclusions: This study report a boy with 46,XX testicular disorder of sex differentiation, showing a de novo partial intragenic duplication of DMRT1. This intragenic duplication may result in a gain of function, acting as primary pro-testis gene (or anti-ovary gene) in a 46,XX human foetus and permitting normal pre-pubertal endocrine testis function.

T Lymphocyte Proliferative Responses Induced by Recombinant Factor VIII in Hemophilia A Patients with Inhibitors

1996 ◽  
Vol 76 (01) ◽  
pp. 017-022 ◽  
Author(s):  
Sylvia T Singer ◽  
Joseph E Addiego ◽  
Donald C Reason ◽  
Alexander H Lucas
Keyword(s):  
T Lymphocytes ◽  
Factor Viii ◽  
Cellular Proliferation ◽  
Mononuclear Cells ◽  
Hemophilia A ◽  
Normal Subjects ◽  
Normal Male ◽  
Cell Fractionation ◽  
Severe Hemophilia ◽  
Human Factor Viii

SummaryIn this study we sought to determine whether factor VUI-reactive T lymphocytes were present in hemophilia A patients with inhibitor antibodies. Peripheral blood mononuclear cells (MNC) were obtained from 12 severe hemophilia A patients having high titer inhibitors, 4 severe hemophilia A patients without inhibitors and 5 normal male subjects. B cell-depleted MNC were cultured in serum-free medium in the absence or presence of 2 µg of recombinant human factor VIII (rFVIII) per ml, and cellular proliferation was assessed after 5 days of culture by measuring 3H-thymidine incorporation. rFVIII induced marked cellular proliferation in cultures of 4 of 12 inhibitor-positive hemophilia patients: fold increase over background (stimulation index, SI) of 7.8 to 23.3. The remaining 8 inhibitor-positive patients, the 4 hemophilia patients without inhibitors and the 5 normal subjects, all had lower proliferative responses to rFVIII, SI range = 1.6 to 6.0. As a group, the inhibitor-positive subjects had significantly higher proliferative responses to rFVIII than did the inhibitor-negative and normal subjects (p < 0.05 by t-test). Cell fractionation experiments showed that T lymphocytes were the rFVIII-responsive cell type, and that monocytes were required for T cell proliferation. Thus, rFVIII-reactive T lymphocytes are present in the peripheral circulation of some inhibitor-positive hemophilia A patients. These T cells may recognize FVIII in an antigen-specific manner and play a central role in the regulation of inhibitor antibody production

Calcium and the Fc Receptor on Human Platelets

1987 ◽  
Vol 57 (03) ◽  
pp. 298-301
Author(s):  
William F Clark ◽  
Gerald J M Tevaarwerk ◽  
Bruce D Reid ◽  
Suzanne Hall ◽  
Anita Caveney ◽  
...  
Keyword(s):  
Specific Binding ◽  
Normal Subjects ◽  
Human Platelets ◽  
Fc Receptor ◽  
Normal Male ◽  
Scatchard Analysis ◽  
Normal Female ◽  
Apparent Difference ◽  
Binding Data ◽  
Direct Binding

SummaryWe have described the calcium dependence of the IgG Fc receptor (Fc-R) on human platelets by analyzing the direct binding of radiolabelled Fc fragments, monomers and dimers of IgG. Specific binding to platelets was undetectable at 37° C in a calcium-free preparation but readily detected when calcium was restored. Scatchard analysis of the binding data for the calcium-restored platelets permitted calculation of the available Fc-R and the Ka of binding for the different IgG ligands. The mean Ka of binding for 12 normal subjects varied from 107 to 108 L/M, with an equal receptor number measured by Fc fragments and dimers of IgG, but a lesser amount for monomeric IgG. There was no apparent difference in Fc-R number for platelets from 6 normal male versus 6 normal female subjects.At 4° C binding was detectable for dimers and polymers of IgG in a calcium-free preparation and this was markedly increased with recalcification. Thus, our data are consistent with an Fc receptor population on human platelets whose avidity for binding is significantly enhanced in a calcium-restored medium.

ÉTUDES IN VIVO SUR LE MÉTABOLISME DES ANDROGÉNES APRES ADMINISTRATION DE STÉROÏDES INHIBITEURS DE L'OVULATION

1965 ◽  
Vol 50 (1) ◽  
pp. 131-144 ◽  
Author(s):  
P. Mauvais-Jarvis ◽  
M. F. Jayle ◽  
J. Decourt ◽  
J. Louchart ◽  
J. Truffert
Keyword(s):  
Luteinizing Hormone ◽  
Urinary Excretion ◽  
Normal Subjects ◽  
Hormone Activity ◽  
Testosterone Production ◽  
Normal Men ◽  
Ethinyl Oestradiol

ABSTRACT Normal subjects and hirsute women with micropolycystic ovaries were treated with ethinyl-oestrenol + 3-methoxy-ethinyl-oestradiol (Lyndiol®), in view of studying the action of this compound on the production of androgens and on the urinary excretion of their metabolites. In normal men, the production of testosterone and the excretion of androsterone and aetiocholanolone are suppressed, whereas the excretion of other 17-ketosteroids and the production of dehydroepiandrosterone sulphate are unchanged. Moreover, the luteinizing hormone activity (LH) in plasma is depressed. It seems that the preparation inhibits specifically the testicular androgen production, by suppressing the hypothalamo-hypophyseal control of LH. Testosterone production and urinary 17-ketosteroid excretion are modified in the same way in women with Stein-Leventhal's syndrome. Physiopathological and therapeutical implications which come from these results are discussed.

scholarly journals Transgenic Chickens Overexpressing Aromatase Have High Estrogen Levels but Maintain a Predominantly Male Phenotype

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Luke S. Lambeth ◽  
Kirsten R. Morris ◽  
Terry G. Wise ◽  
David M. Cummins ◽  
Terri E. O'Neil ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Sex Differentiation ◽  
Serum Levels ◽  
Sex Reversal ◽  
High Serum ◽  
Small Sample ◽  
Chicken Embryos ◽  
Sex Development ◽  
Multistep Process ◽  
Transgenic Chickens

Abstract Estrogens play a key role in sexual differentiation of both the gonads and external traits in birds. The production of estrogen occurs via a well-characterized steroidogenic pathway, which is a multistep process involving several enzymes, including cytochrome P450 aromatase. In chicken embryos, the aromatase gene (CYP19A1) is expressed female-specifically from the time of gonadal sex differentiation. Ectopic overexpression of aromatase in male chicken embryos induces gonadal sex reversal, and male embryos treated with estradiol become feminized; however, this is not permanent. To test whether a continuous supply of estrogen in adult chickens could induce stable male to female sex reversal, 2 transgenic male chickens overexpressing aromatase were generated using the Tol2/transposase system. These birds had robust ectopic aromatase expression, which resulted in the production of high serum levels of estradiol. Transgenic males had female-like wattle and comb growth and feathering, but they retained male weights, displayed leg spurs, and developed testes. Despite the small sample size, this data strongly suggests that high levels of circulating estrogen are insufficient to maintain a female gonadal phenotype in adult birds. Previous observations of gynandromorph birds and embryos with mixed sex chimeric gonads have highlighted the role of cell autonomous sex identity in chickens. This might imply that in the study described here, direct genetic effects of the male chromosomes largely prevailed over the hormonal profile of the aromatase transgenic birds. This data therefore support the emerging view of at least partial cell autonomous sex development in birds. However, a larger study will confirm this intriguing observation.

In vivo quantification of pulmonary beta-adrenoceptor density in humans with (S)-[11C]CGP-12177 and PET

1993 ◽  
Vol 75 (2) ◽  
pp. 559-565 ◽  
Author(s):  
J. Ueki ◽  
C. G. Rhodes ◽  
J. M. Hughes ◽  
R. De Silva ◽  
D. C. Lefroy ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Specific Activity ◽  
Regional Distribution ◽  
High Specific Activity ◽  
Normal Subjects ◽  
Normal Male ◽  
Tissue Density ◽  
Beta Adrenoceptor ◽  
Cgp 12177

The in vivo regional distribution of pulmonary beta-adrenoceptors was imaged and quantified in humans with the hydrophilic beta-adrenoceptor antagonist (S)-CGP-12177 labeled with carbon-11 [(S)-[11C]CGP-12177] and positron emission tomography (PET). Six normal male volunteers and eight patients with hypertrophic cardiomyopathy were studied. PET scanning consisted of transmission (tissue density), C15O (blood volume), and (S)-[11C]CGP-12177 (beta-adrenoceptor) emission scans. High-specific-activity (S)-[11C]-CGP-12177 (7.1 +/- 2.0 micrograms, 6.5 +/- 2.1 GBq/mumol) was given intravenously followed by a low-specific-activity (S)-[11C]CGP-12177 injection (34.0 +/- 4.8 micrograms, 2.3 +/- 0.8 GBq/mumol). Binding capacity (Bmax) was calculated in each region of interest as picomoles per gram by normalizing it to the local extravascular tissue density. In normal subjects, average Bmax for all regions of interest was 14.8 +/- 1.6 (SD) pmol/g, which is similar to previously reported in vitro values. In both groups there were no differences in beta-adrenoceptor density between peripheral and central regions nor between right and left lungs. In patients with hypertrophic cardiomyopathy, extravascular tissue density was 24% higher than in normal subjects; Bmax per milliliter thoracic volume was correspondingly higher but was not different from that in normal subjects when expressed per gram tissue (15.8 +/- 2.6 pmol/g). These data suggest that in vivo beta-adrenoceptor density may be quantifiable in humans with the use of PET. This should offer a means to study physiological regulation through repeat measurements.

Effects of galvanic mastoid stimulation in seated human subjects

2009 ◽  
Vol 106 (3) ◽  
pp. 893-903 ◽  
Author(s):  
Z. Ghanim ◽  
J. C. Lamy ◽  
A. Lackmy ◽  
V. Achache ◽  
N. Roche ◽  
...  
Keyword(s):  
Human Subjects ◽  
Normal Subjects ◽  
Standing Position ◽  
Reflex Response ◽  
Emg Activity ◽  
Free Standing ◽  
Vestibular Response ◽  
Vestibular Reflex ◽  
Tendon Jerk ◽  
Biphasic Responses

The vestibular responses evoked by transmastoid galvanic stimulation (GS) in the rectified soleus electromyogram (EMG) in freely standing human subjects disappear when seated. However, a GS-induced facilitation of the soleus monosynaptic (H and tendon jerk) reflex has been described in few experiments in subjects lying prone or seated. This study addresses the issue of whether this reflex facilitation while seated is of vestibulospinal origin. GS-induced responses in the soleus (modulation of the rectified ongoing EMG and of the monosynaptic reflexes) were compared in the same normal subjects while freely standing and sitting with back and head support. The polarity-dependent biphasic responses in the free-standing position were replaced by a non-polarity-dependent twofold facilitation while seated. The effects of GS were hardly detectable in the rectified ongoing voluntary EMG activity, weak for the H reflex, but large and constant for the tendon jerk. They were subject to habituation. Anesthesia of the skin beneath the GS electrodes markedly reduced the reflex facilitation, while a similar, although weaker, facilitation of the tendon jerk was observed when GS was replaced with purely cutaneous stimulation, a tap to the tendon of the sternomastoid muscle, or an auditory click. The stimulation polarity independence of the GS-induced reflex facilitation argues strongly against a vestibular response. However, the vestibular afferent volley, insufficient to produce a vestibular reflex response while seated, could summate with the GS-induced tactile or proprioceptive volley to produce a startle-like response responsible for the reflex facilitation.

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