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M Rivarola

Publications and source records attributed to M Rivarola.

14 recordsLinked to original sources
PubMed1999

Smith-Lemli-Opitz syndrome: in vivo and in vitro study of testicular function in a prepubertal patient with ambiguous genitalia.

The pathogenesis of the development of ambiguous genitalia reported in some 46,XY patients with Smith-Lemli-Opitz syndrome is not understood. Presumably, it is related to the 7-dehydrocholesterol reductase deficiency present in these patients. In this study we have evaluated testicular function, both in vivo and in vitro, in a 46,XY patient with ambiguous genitalia, reared as a girl. The diagnosis was based on clinical features, low serum cholesterol and high serum 7-dehydrocholesterol levels. Serum hormone values, determined during the first month of age, showed normal basal testosterone (1.95 ng/ml), LH (0.91 U/l) and FSH (2.51 U/l). However, serum testosterone did not increase after hCG administration (1.98 ng/ml). On the other hand, the patient had a positive biological response to exogenous testosterone (decrease in sex hormone-binding globulin serum levels). She was orchidectomized at the age of 33 mo. Testicular cells were dispersed and maintained in culture for 6 d. These cells showed a very good capacity to secrete testosterone into the culture medium (X +/- SD, 26.1 +/- 11.7 vs. 4.36 +/- 1.70 pmol/10(6) cells/24 h in a control group of testicular cells prepared from testes collected at necropsy). The patient's cells failed to respond to LH stimulation (18.6 +/- 4.0 pmol/10(6) cells/24 h), although they did respond to other stimuli. It is concluded that the severe cholesterol deficiency of this patient did not impair the capacity of the testes to synthesize testosterone. However, the LH/hCG receptor or its subsequent message was activated neither in vivo nor in vitro. This finding suggests that the foetal testes might have failed to respond to placental hCG at the time of male external genital differentiation. This failure could have been responsible for the ambiguous genitalia present in this patient.

Cells, Cultured↗
PubMed1999

[Role of 3 beta hydroxysteroid dehydrogenase (3 beta HSD) in human adrenal androgen synthesis].

Adrenarche is the maturational increase of adrenal androgens that takes place in 6-8 year old children. In order to study the role of 3 beta HSD in the regulation of the synthesis of human adrenal androgens, the abundance of 3 beta HSD mRNA (Dot Blot and semiquantitative RT-PCR) was measured in 11 human prepubertal and early pubertal adrenal tissues. Subjects were divided in 2 age groups (Gr): Gr1, < 8 years (y) old (n = 6, range 0.1-2.5) and Gr2, > or = 8 y old (n = 5, range 8.0-13.0). Tissue from one adrenal tumor with Cushing's syndrome (TSC) and 2 virilizing adrenal tumors (TV), as well as adrenal cells prepared from the TSC and from 1 TV were also studied. They were maintained in culture for 3 days in basal conditions (BC) and under ACTH and IGF-1 stimulation. mRNA in Gr1 was higher than in Gr2 (Dot blot: 4.65 +/- 2.70 and 0.28 +/- 0.27 AU, p = 0.006; RT-PCR: 21.5 +/- 12.5 and 6.77 +/- 3.78 AU, p = 0.039, respectively). 3 beta HSD mRNA in TSC (8.74 +/- 1.74) was higher than in the 2 TVs (0.47 +/- 0.02 and 0.87 +/- 0.08) p = 0.001. In TSC cells, basal mRNA (0.82 +/- 0.10) decreased under ACTH (0.55 +/- 0.06), p = 0.005, and increased under IGF-1 (2.36 +/- 0.07), p = 0.006. No changes were observed in TV cells. On day 3, TV cells in BC secreted 1170.0 +/- 210.0 and 335.0 +/- 29.0 pmol/10(6) cells in 24 hs of DHEAS and androstenedione, while TSC cells secreted 17.1 +/- 3.5 and 73.7 +/- 11.7, respectively. Values increased under ACTH in TV cells (2006.0 +/- 360.0 and 525.0 +/- 76.0) and in TSC cells (29.8 +/- 5.4 and 366.8 +/- 129) p < 0.05, but they decreased under IGF-1 only in TSC cells (7.9 +/- 2.4 and 43.7 +/- 6.1) p < 0.05. These data support the hypothesis that human adrenarche could be secondary to a decrease of 3 beta HSD mRNA. Our finding that when 3 beta HSD mRNA decreases androgen secretion increases (ACTH) and when 3 beta HSD mRNA increases androgen secretion decreases (IGF-1), strongly suggests that 3 beta HSD has a modulatory role in adrenal androgen steroidogenesis.

3-Hydroxysteroid Dehydrogenases↗
PubMed1997

Report of an XX male with hypospadias and pubertal gynecomastia, SRY gene negative in blood leukocytes but SRY gene positive in testicular cells.

Most XX male subjects present an anomalous translocation of the sex-determining region of the chromosome Y (SRY) gene from chromosome Y to chromosome X. Several explanations have been proposed for the differentiation of testicular tissue in the absence of SRY gene. A patient is presented in whom the SRY gene was absent in peripheral leukocytes but present in testicular tissue. This possibility should always be ruled out before diagnosing Y-negative XX maleness.

Adolescent↗
PubMed1989

Decrease of serum sex hormone-binding globulin as a marker of androgen sensitivity. Correlation with clinical response.

An evaluation of the usefulness of determining the decrease in serum sex hormone-binding globulin after exogenous testosterone was studied in 55 prepubertal patients with ambiguous external genitalia or micropenis. The biochemical response (androgen sensitivity test) was compared with the clinical response as judged by signs of androgen stimulation of external genitalia. Patients were divided in two groups according to age. Group I, 11 patients younger than 3 months and Group II, 44 patients older than 3 months. Only in 54% of Group I was there a correlation between the androgen sensitivity test and the clinical response to androgens in either a positive (4 patients) or negative sense (2 patients). On the other hand, the androgen sensitivity test and the clinical response to androgens correlated in 91% of the patients of Group II in either a positive (35 patients) or negative sense (5 patients). Two of the 4 patients with lacking correlation had a negative androgen sensitivity test and micropenis secondary to pituitary deficiency. It is concluded that in prepubertal patients older than 3 months with abnormalities of sex differentiation, the androgen sensitivity test and the clinical response to androgens are useful for evaluating androgen sensitivity. The clinical response to androgens is useful in early life when a positive response is found.

Chorionic Gonadotropin↗
PubMed1987

Long-term endocrine sequelae after surgery, radiotherapy, and chemotherapy in children with medulloblastoma.

Thirteen children with medulloblastoma, were studied after 2 to 62 months off radiotherapy and chemotherapy with methotrexate and BCNU. Ages at time of study ranged from 2.3 to 15.7 years. Eleven patients, followed for a mean of 22 months, showed a significant decrease of height score, whereas nine patients had deficient growth hormone (GH) response to provocative tests. Clinical pubertal progression was normal in all patients, and three of five girls with advanced pubertal development had menarche. No evidences of gonadotropin disturbances were found in five patients whereas seven had raised basal follicle-stimulating hormone (FSH) level or FSH response to luteinizing hormone-releasing hormone (LH-RH). Abnormalities in thyrotrophin (TSH) secretion were found in 9 of 13 patients. This study shows that poor growth and GH deficiency were frequent in our patients. The high frequency of thyroid disturbances observed point out the need of evaluating thyroid function for adequate replacement therapy. Perhaps modification of adjuvant chemotherapy in the future can diminish drug-induced gonadal damage.

Adolescent↗
PubMed1982

Androgen binding to subcellular particles of rat testis.

Androgen binding activity was evaluated in different subcellular particulate fractions obtained by differential centrifugation of 32-day-old rat seminiferous tubules homogenates. After eliminating heavy particles by centrifugation at 4300 g during 4 min in 0.25 M sucrose buffer, a 27,000 g pellet was obtained and layered on 1.05 M sucrose buffer. The relatively light particulate interface (LPF) formed during centrifugation at 27,000 g 60 min, showed the highest androgen binding activity among particulate fractions. This binding was associated with the plasma membrane marker 5'-nucleotidase and it did not follow any of six other subcellular structure markers: DNA for nuclei, succinate dehydrogenase for mitochondria, acid phosphatase for lysosomes, NADPH-cytochrome C reductase for smooth endoplasmic reticulum, RNA for rough endoplasmic reticulum and lactate dehydrogenase for cytosol. In LPF, concentrations of sites were estimated to be 328 +/- 54 fmol per mg proteins and affinity constant 0.78 +/- 0.23 10(9) M-1. Heat stability, steroid specificity, affinity constant and rate of dissociation were similar to the well known androgen binding protein, ABP. Presence of ABP or a similar protein in subcellular particles might play a role in the mechanism of action of androgens in seminiferous tubules of maturing rats.

Androgens↗
PubMed1981

Testicular function in prepubertal male pseudohermaphroditism.

Testicular function was evaluated in forty-one prepubertal patients with male pseudohermaphroditism by determining serum concentrations of progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone and dihydrotestosterone before and after stimulation with hCG and, in some instances, ACTH. Testosterone response to hCG was normal in all subjects. In one patient, a 4-year-old boy, a deficiency of 17,20-desmolase activity was diagnosed based on the coexistence of elevated levels of pregnenolone, 17-hydroxypregnenolone, progesterone and 17-hydroxyprogesterone and low levels of dehydroepiandrosterone and androstenedione. In three other patients enzymatic blocks were suspected but not confirmed. Congenital deficiency of enzymes necessary for testosterone biosynthesis is an uncommon aetiology of male pseudohermaphroditism.

Adolescent↗
PubMed1979

Testicular function in post pubertal male pseudohermaphroditism.

Testicular endocrine function was studied in twelve post pubertal patients with male pseudohermaphroditism and 46 XY chromosomal constitution. Patients were divided into three groups, four subjects who became feminized during puberty, five who became masculinized during puberty and three who were castrated before puberty. Serum dehydroepiandrosterone, progesterone, 17-hydroxyprogesterone, androstendione, testosterone, dihydrotestosterone, LH and FSH were determined by radioimmunoassay. Patients of the first group had the clinical characteristics of testicular feminization secondary to absence of the androgen receptor. One of the five patients of the second group had deficient testosterone secretion but no enzymatic defect could be demonstrated. One of the subjects castrated before puberty had a deficiency in 17,20-desmolase. Therefore, evidence of a failure of the fetal testes could be found in only two of the twelve patients studied.

Adolescent↗
PubMedDate not supplied

Mutations of the steroid 21-hydroxylase gene in an Argentinian population of 36 patients with classical congenital adrenal hyperplasia.

In several studies carried out in USA and Europe, gene deletions, large gene conversions and six point mutations accounted for over 90% of the mutated alleles reported in classical congenital hyperplasia (CAH). In order to know the relative frequencies of mutations in a Latin-American population, the CYP21 active gene was analyzed in 42 patients with CAH belonging to 36 families attending two Argentinian clinics. The salt wasting form was diagnosed in 24 index cases and the simple virilized form in 12. When available, parents were also studied. DNA was extracted from peripheral blood leukocytes and specific PCR amplification of four different fragments of the CYP21 gene was carried out, followed by electrophoresis of the amplified product. The four fragments include segments of the gene containing the six most frequently reported abnormalities in classical CAH: IN2, EX3, R356W, cluster EX6 and I172N. Point mutations were studied by allelic specific oligonucleotide hybridization; Q318X was studied by digestion of the PCR product with PsT1 restriction enzyme and electrophoresis on 6% non-denaturing polyacrylamide gels. Deletions and macroconversions as well as confirmation of homozygote point mutations were studied by Southern blotting. Percentage distribution of abnormalities was as follows: deletion/macroconversion 18, IN2 18, I172N 15.3, Q318X 13.8, R356W 5.5, EX3 2.7, cluster EX6 0, not characterized 26.7. The complete genotype could be determined in 20 families while in 12 additional ones, the mutation was detected in one allele. Deletion/macroconversion, IN2, EX3 and Q318X were detected more frequently in salt wasting patients while I172N and R356W were found in simple virilized patients. However, genotype was not always concordant with phenotype. It is concluded that there are differences in the frequency of several gene mutations and in that of deletion/macroconversion between this Latin-American population and several reported American and European populations. In particular the percentage of deletion/macroconversion, IN2, EX3 and cluster EX6 was lower while I172N was higher in our Latin-American population. Furthermore the frequency of mutations not characterized was larger. This information is useful to delineate appropriate strategies for prenatal diagnosis in this particular population.

Adrenal Hyperplasia, Congenital↗