Biomedical subjects

L Poretsky

Publications and source records attributed to L Poretsky.

23 records · Page 2Linked to original sources

PubMed1987

Ketoconazole reverses hyperandrogenism in a patient with insulin resistance and acanthosis nigricans.

We administered ketoconazole to a young woman with ovarian hyperandrogenism, insulin resistance, and acanthosis nigricans. While taking ketoconazole, her serum testosterone, androstenedione, dehydroepiandrosterone, and cortisol levels declined, while serum progesterone, 17-hydroxyprogesterone, and 11-deoxycortisol rose. Serum LH, FSH, and estradiol levels were intermittently higher during ketoconazole treatment, although LH and FSH responsiveness to GnRH did not change. Basal and stimulated serum insulin concentrations were high before and during ketoconazole therapy, while fasting glucose levels and glucose disappearance rate constants were normal throughout the study. A dramatic improvement in hirsutism occurred, and menses resumed after a 6-yr hiatus. Adverse drug effects or clinical evidence of adrenal insufficiency were not encountered. These results support a role for ketoconazole in the therapy of ovarian hyperandrogenism.

Acanthosis Nigricans↗

PubMed1987

Characterization of insulin-like growth factor binding to human granulosa cells obtained during in vitro fertilization.

Insulin and IGF-I affect in vitro ovarian stromal and follicular cell function in several species. We previously characterized insulin receptors on human granulosa cells obtained from in vitro fertilization procedures but were unable to demonstrate specific binding of IGF-I. Following modification of the assay conditions, we now report specific, high affinity IGF-1 binding sites on human granulosa cells. Substitution of equimolar concentrations of sucrose for sodium chloride in the buffer solution increased binding of IGF but not insulin in equilibrium assays. Maximal specific IGF-I binding was 2.69 +/- 0.30%/10(5) cells (SEM, n = 9) with half-maximal inhibition of binding at 2 ng/ml IGF-I. Unlabeled insulin recognized the type I IGF receptor with low affinity. An IGF-I receptor monoclonal antibody (alpha IR-3) inhibited 125I-IGF-I but not 125I-insulin binding. Affinity crosslinking followed by SDS/PAGE under reducing conditions revealed IGF-I binding at a molecular weight compatible with the alpha subunit of the type I IGF receptor and with a pattern of inhibition by various ligands that paralleled the equilibrium binding assays. IGF-I receptors are present on freshly isolated human ovarian granulosa cells obtained following pharmacologic stimulation with gonadotrophin according to the protocols of in vitro fertilization. The biologic function of these receptors currently is being investigated.

Affinity Labels↗

PubMed1986

Primary amenorrhea and pseudoprolactinoma in a patient with primary hypothyroidism. Reversal of clinical, biochemical, and radiologic abnormalities with levothyroxine.

A 15-year-old girl presented with primary amenorrhea, galactorrhea, hyperprolactinemia and an enlarged pituitary gland. She proved to have primary hypothyroidism. Therapy with levothyroxine resulted in prompt induction of regular menses, normalization of hormone levels, and a reduction in the size of the pituitary. Although hypothyroidism is known to produce secondary amenorrhea, hyperprolactinemia, and pituitary enlargement, this is believed to be the first computed tomographic documentation of such a "pseudoprolactinoma" presenting as primary amenorrhea.

Adolescent↗

PubMed1985

The diagnosis of myocardial infarction by computer-derived protocol in a municipal hospital.

The evaluation of an emergency room patient with acute chest pain is often difficult. Recently, computers have been employed to develop protocols for identifying which patients are likely to have acute myocardial infarctions and to benefit, therefore, from admission to a relatively scarce coronary care unit bed. We have tested the latest computer-derived instrument in a municipal hospital and found it to be less reliable than the clinical judgement of physicians.

Adult↗

PubMed1985

Distribution and characterization of insulin and insulin-like growth factor I receptors in normal human ovary.

Insulin-resistant hyperinsulinemic states are now widely known to be associated with ovarian hyperandrogenism, and this is thought to be due to an action of insulin on the ovary. However, the identity of the receptor that is responsible for insulin action in these patients, whose insulin receptors on classical target tissues are severely impaired, is unclear. We now report the presence of insulin receptors in stromal and follicular compartments as well as in granulosa cells obtained from normal ovaries. After 15-h incubations at 4 C with [125I]insulin and tissue fragments, specific insulin binding was 6-19% and 7-13%/mg protein (n = 8) to stroma and theca, respectively. Granulosa cells obtained in the course of in vitro fertilization were separated from red cells on a Percoll gradient; specific insulin binding ranged from 9-15%/10(6) cells. Insulin binding was characterized by sensitive insulin competition (half-maximal, 10 ng/ml), appropriately shifted proinsulin competition (20 times to the right), and complete inhibition by specific anti-insulin receptor antibodies (B-2). An antibody to the insulin-like growth factor I (IGF-I) receptor (alpha IR-3) that inhibits IGF-I binding to IGF-I receptors in other cell systems had no effect on insulin binding. Further proof that this binding is to classic insulin receptors was obtained from measurement of insulin-stimulated receptor autophosphorylation. When insulin receptors from stroma were extracted with Triton X-100 and incubated with [gamma-32P]ATP and Mn, insulin increased the incorporation of 32P into the beta-subunit of the receptor 5-fold. In parallel studies with [125I-]IGF-I and specific blocking antibodies to its receptor, no detectable IGF-I binding to stroma or follicles was found. We conclude that specific high affinity insulin receptors possessing tyrosine kinase activity are widely distributed in normal human ovary. IGF-I receptors in normal ovary are either absent or present at very low density. Binding of insulin to its own receptor (as opposed to IGF-I receptors) appears to be the most likely first step in the stimulation of ovarian steroidogenesis by insulin in normal ovaries and possibly in insulin-resistant states as well.

Adult↗