PubMed Health⌕ Search

Biomedical subjects

Julianne Imperato-McGinley

Publications and source records attributed to Julianne Imperato-McGinley.

11 recordsLinked to original sources
PubMed2006

Bone mineral density in the complete androgen insensitivity and 5alpha-reductase-2 deficiency syndromes.

CONTEXT: Subjects with complete androgen insensitivity (CAI) and 5alpha-reductase-2 deficiency (5alphaRD-2) are natural human models to study the direct effect of androgens on bone mineral density (BMD). OBJECTIVE: The objective of this study was to test the hypothesis that androgens have a direct effect on BMD in men. DESIGN: This was a prospective, observational study (1989-1999) using dual energy x-ray absorptiometry. SETTING: The study was set in an outpatient specialty referral center. PATIENTS OR OTHER PARTICIPANTS: All known subjects with these conditions (12 CAI and 16 5alphaRD-2) from diverse sociodemographic backgrounds were recruited for the study. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURE: Mean Z score and weight-matched Z score at lumbar spine and femoral neck for CAI and 5alphaRD-2 subjects were determined. RESULTS: Twelve CAI subjects had mean Z score at L2-L4 of -2.84 (+/-0.97, P < 0.001) and a mean weight-matched Z score of -2.52 (+/-0.94, P < 0.001). The mean Z score at the femoral neck was -1.33 (+/-0.91, P < 0.001) and the mean weight-matched Z score was -1.10 (+/-0.82, P = 0.001). Sixteen 5alphaRD-2 subjects had a mean Z score at L2-L4 of -0.84 (+/-1.29, P = 0.02) and a mean weight-matched Z score for 15 of 16 patients of -0.44 (+/-1.08, P = 0.14). The mean Z score at the femoral neck was 0.14 (+/-1.02, P = 0.58) and the mean weight-matched Z score for 15 of 16 patients was 0.49 (+/-0.94, P = 0.06). Therefore, in CAI subjects, BMD was significantly decreased in the spine and hip. 5alphaRD-2 subjects had normal BMD values. CONCLUSIONS: 1) Androgens are of direct importance in the development and/or maintenance of BMD; and 2) testosterone and/or low levels of dihydrotestosterone appear to be sufficient for BMD development and/or maintenance.

Absorptiometry, Photon↗
PubMed2006

Sex differences in mental rotation: top-down versus bottom-up processing.

Functional MRI during performance of a validated mental rotation task was used to assess a neurobiological basis for sex differences in visuospatial processing. Between-sex group analysis demonstrated greater activity in women than in men in dorsalmedial prefrontal and other high-order heteromodal association cortices, suggesting women performed mental rotation in an effortful, "top-down" fashion. In contrast, men activated primary sensory cortices as well as regions involved in implicit learning (basal ganglia) and mental imagery (precuneus), consistent with a more automatic, "bottom-up" strategy. Functional connectivity analysis in association with a measure of behavioral performance showed that, in men (but not women), accurate performance was associated with deactivation of parieto-insular vestibular cortex (PIVC) as part of a visual-vestibular network. Automatic evocation by men to a greater extent than women of this network during mental rotation may represent an effective, unconscious, bottom-up neural strategy which could reasonably account for men's traditional visuospatial performance advantage.

Brain↗
PubMed2006

Regulation of prostate 5alpha-reductase-2 gene expression and prostate weight by dietary fat and caloric intake in the rat.

BACKGROUND: High-fat diet is a major risk factor for prostate cancer. 5alpha-reductases are potential targets of dietary fat. METHODS: Male ACI/Seg rats given either a low-fat or a high-fat diet at weaning or adulthood were sacrificed at 2, 4, and 10 weeks after dietary treatment. Prostate 5alpha-reductase mRNAs, plasma androgens, food consumption, prostate, and body weight were determined. RESULTS: Prostate 5alpha-reductase-2 mRNA and plasma dihydrotestosterone levels were elevated at 2 weeks, and prostate weight was increased at 10 weeks in neonatal rats fed the high-fat diet. Animals fed the high-fat diet consumed more calories in the first 4 weeks. 5alpha-reductase-1 mRNA, plasma testosterone, and body weight were not different between the two dietary groups. These dietary effects were not observed in adult rats fed the same diets. CONCLUSION: A high-dietary fat and caloric intake upregulates prostate 5alpha-reductase-2 gene expression, and stimulates prostate growth in neonatal, but not adult rats.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2006

The relation between computerized and paper-and-pencil mental rotation tasks: a validation study.

The present study aimed at validating a computerized mental rotation task developed for use in functional Magnetic Resonance Imaging (fMRI) studies. Eighty-three females and 74 males completed the computerized task, two pencil-and-paper tests of mental rotation, and reported their high school grades in mathematics, English, and history. The computerized task involved the presentation of pairs of three-dimensional stimuli that differed in orientation by 0, 40, 80, 120, or 160 degrees. Results showed significant gender differences in favor of males in the three main tasks, although gender interacted with angle of rotation in the computerized task. Evidence for concurrent validity was obtained in the form of significant correlations between performance on tasks relevant to mental rotation (paper and pencil tests and mathematics grades), whereas discriminant validity was demonstrated by a lack of correlation with tasks deemed irrelevant to mental rotation (English and history grades). These findings support the use of our computerized mental rotation task as a valid measure of mental rotation abilities in fMRI studies.

Adolescent↗
PubMed2004

Gender identity in XY intersexuality.

The following syndromes of XY intersexuality are reviewed: 5alpha-reductase-2 deficiency, 17beta-hydroxysteroid dehydrogenase-3 deficiency, and complete and partial androgen insensitivity with attention focused on issues of gender identity. Each syndrome, with its unique presentation, provides an opportunity to explore the relative effects of nature (androgens) versus nurture (sex of rearing) in gender identity development. The phenomenon of gender role reversal in these conditions is described and theories on the determinants of gender identity formation are proposed. Issues of importance to psychiatrists in treating patients who have these conditions also are discussed.

17-Hydroxysteroid Dehydrogenases↗
PubMed2004

Fetal hormones and sexual differentiation.

The process of fetal sexual differentiation, which involves establishment of genetic sex, differentiation of the gonads, and development of phenotypic sex, is summarized. The morphologic changes that occur in utero that lead to development of the male and female gonads, germ cells, reproductive tracts, and external genitalia are described. Most of the article focuses on the hormones that regulate sexual differentiation and development in utero. The genetic factors that regulate sexual differentiation, which constitute a new and emerging field, also are discussed.

Cell Differentiation↗
PubMed2004

Long-term growth hormone therapy in adulthood results in significant linear growth in siblings with a PROP-1 gene mutation.

PROP-1 gene mutations result in impaired production of GH, gonadotropins, TSH, and prolactin. We describe three adult siblings, aged 18-25 yr, with short stature, hypothyroidism, and lack of pubertal maturation, who were homozygous for 301-302delAG PROP-1 mutation. We had the unique opportunity to treat them in adulthood with GH for 4-5 yr and thyroid replacement before sex steroid replacement. Sibling 1, a female, had a chronological age (CA) of 25 yr 8 months, a bone age (BA) of 12.5 yr, and height of 128.7 cm [-5.29 sd score (SDS)]; sibling 2, a younger sister had a CA of 22 yr 5 months, a BA of 13 yr, and height of 137.5 cm (-3.94 SDS); and sibling 3, a male, had a CA of 18 yr 4 months, a BA of 11.5 yr, and height of 127.5 cm (-6.38 SDS). Despite delay in treatment and fairly advanced BA, all responded to GH and thyroid hormone therapy with a dramatic increase in linear growth: 22.3 cm for sibling 1, 22 cm for sibling 2, and 34.5 cm for sibling 3. After sex hormone replacement, siblings 1, 2, and 3 grew another 2.6, 3, and 9.5 cm to final heights of 153.6, 162.5, and 171.5 cm, respectively. In conclusion, the substantial linear growth in adult siblings with a PROP-1 mutation illustrates that despite an advanced BA, linear growth potential remains in adulthood in the setting of sex steroid deficiency.

Adolescent↗
PubMed2003

Mutations in CYP11B1 gene: phenotype-genotype correlations.

11beta-hydroxylase deficiency, an autosomal recessive disorder, is the second most common cause of congenital adrenal hyperplasia. We studied four subjects with classic 11beta-hydroxylase deficiency and severe hypertension: a 46,XX affected subject from a Turkish family with severe ambiguity of the external genitalia and hypertension, and three affected 46,XY subjects from a Dominican kindred with isosexual precocious puberty and severe hypertension. The affected subjects had significantly elevated plasma 11-desoxycortisol, 11-desoxycorticosterone, Delta4-androstenedione, and testosterone. To determine the molecular genetic defects, genomic DNA was isolated from the leukocytes of affected subjects and their family members. The encoding region of the 11beta-hydroxylase gene (CYP11B1) was amplified by PCR with specific primers. Using single-stranded DNA conformational polymorphism (SSCP) and DNA sequencing, a nonsense mutation in exon 6 of CYP11B1 in the affected 46,XX subject from the Turkish family was identified, where a cytosine was substituted by a thymidine, resulting in the replacement of glutamine (CAG) by a stop codon (TAG) at amino acid position 338 (Q338X). In the three 46,XY Dominican boys, the mutation was also a nonsense mutation in exon 6 of CYP11B1, where a cytosine was substituted by a thymidine, resulting in the replacement of glutamine (CAG) by a stop codon (TAG) at amino acid position 356 (Q356X). Both mutations result in the biosynthesis of a truncated 11beta-hydroxylase protein with loss of enzymatic activity. Heterozygosity was determined in family members of both probands including parents and siblings. These results indicate that mutations of CYP11B1 in these subjects are responsible for their clinical syndromes.

Adrenal Hyperplasia, Congenital↗
PubMedDate not supplied

Androgen-induced prostate-specific antigen gene expression is mediated via dihydrotestosterone in LNCaP cells.

Prostate cancer is a leading cause of cancer death in American males. Androgens play an essential role in prostate development, growth and pathogenesis of benign prostate hyperplasia, and prostate cancer. Although testosterone is the main androgen secreted from the testes, dihydrotestosterone (DHT), a more potent androgen converted from testosterone by 5alpha-reductase isozymes, type 1 and 2, is the major androgen in the prostate cells. Thus, 5alpha-reductase(s) are critical in determining androgen activity in the prostate. However, it is unclear in prostate tumor cells whether 1 or 2 5alpha-reductase isozymes are expressed and whether they are functionally important. In the present report, we studied the importance of 5alpha-reductase isozymes in the androgen induction of prostate-specific antigen (PSA) gene expression in LNCaP prostatic tumor cells. Treatment with either testosterone or DHT in LNCaP cells produced dose- and time-dependent increases in PSA levels in the cell media and in PSA messenger RNA (mRNA) levels in the cells. However, testosterone-induced but not DHT-induced PSA gene expression was significantly inhibited by finasteride, a 5alpha-reductase inhibitor, in a dose-dependent manner. Furthermore, we demonstrated for the first time that both 5alpha-reductase-1 and 5alpha-reductase-2 mRNAs were expressed in LNCaP cells using reverse transcriptase-polymerase chain reaction (RT-PCR) and RT-PCR Southern blot analysis. These results suggest that both 5alpha-reductase isozymes are present and functionally important in prostatic tumor LNCaP cells and that DHT is a major mediator of androgen induction of PSA gene expression in these cells.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMedDate not supplied

The Chinese medicinal herbal formula ZYD88 inhibits cell growth and promotes cell apoptosis in prostatic tumor cells.

Prostate cancer is a leading cause of cancer death in American males. Currently, there is no curative therapy available once prostate cancer has metastasized. A major systemic therapy for metastatic prostate cancer is anti-androgen therapy. Unfortunately this therapy is only palliative and rarely curative, and eventually the tumor cells develop resistance to further hormone manipulation. It is therefore imperative to develop alternative effective therapies. In the present study, the effect of a Chinese herbal formula, ZYD88, on regulation of cell growth and cell apoptosis was examined in prostatic tumor cells. ZYD88 decreased cell viability of multiple prostatic tumor cell lines, DU-145, PC-3, MDA-PCa 2b and LNCaP in a time- and dose-dependent manner. It also produced a rapid and dose-dependent increase in caspase 3 activity in LNCaP and PC-3 cells, and induced DNA fragmentation in LNCaP cells, indicating cell apoptosis. In cotransfection assays, ZYD88 inhibited androgen-induced prostate specific antigen (PSA) gene promoter activity, and induced estrogen-target gene promoter activity. These data suggest that ZYD88 is a potential agent for prostate cancer therapy, and deserves further study.

Apoptosis↗