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S Malozowski

Publications and source records attributed to S Malozowski.

46 records · Page 3Linked to original sources
PubMed1987

Identification and characterization of two classes of receptors for oxytocin and vasopressin in porcine tunica albuginea, epididymis, and vas deferens.

The neurohypophysial hormones oxytocin (OT) and vasopressin (VP) are involved in the regulation of the contractility of the male genital tract in several animal species. We investigated the presence of specific binding sites for [3H]OT and [3H]arginine VP (AVP) in membranes prepared from tunica albuginea, epididymis, and vas deferens from prepubertal pigs 2-16 weeks of age. Membranes were incubated with [3H]OT and [3H]AVP in the presence or absence of the corresponding unlabeled peptides. Binding equilibrium was reached in 60 min at 22 C. Millimolar concentrations of Mg2+ increased the specific binding of both ligands. Analysis of families of self- and cross-displacement curves using the computer program LIGAND clearly demonstrated that two classes of binding sites were present in all tissues investigated. The first class of sites, designated the OT site, shows high affinity for OT, AVP, lysine vasopressin, arginine vasotocin, the selective OT agonists [Thr4,Gly7]OT and [Asu1,6]OT, and the OT antagonists derived from ornithine vasotocin (OVT), namely d(CH2)5Tyr(Et)OVT and dEt2OVT. The second class of sites, designated the VP site, shows high affinity for AVP, lysine vasopressin, arginine vasotocin, and the selective V1 antagonist d(CH2)5Tyr(Me)AVP. The V2 agonist [1-deamino,4-valine]8-D-AVP shows low affinity for both sites. Isotocin, desglycinamide [Arg-8]AVP and tocinoic acid were ineffective in displacing [3H]AVP or [3H]OT. The highest density of OT receptors was found in tunica albuginea and epididymis, whereas the highest density of AVP receptors was found in vas deferens. Adenylate cyclase was not activated in any of the tissues studied by concentrations of AVP or OT up to 100-fold greater than their Kd values. This is the first demonstration and pharmacological characterization of specific OT and V1 VP receptors in the tunica albuginea, epididymis, and vas deferens. The recent demonstration of high local concentration of neurohypophysial hormones in the gonads of several mammals support a physiological role of these OT and VP receptors in regulation of the motility of the male genital tract.

Animals↗
PubMed1987

Growth hormone-releasing hormone: therapeutic perspectives.

Growth hormone-releasing hormone (GHRH), the hypothalamic peptide which stimulates the release of growth hormone (GH) from the pituitary, has been the center of intense study since its structure was described in 1982. It is in the area of growth hormone deficiency (GHD) that GHRH has its greatest clinical potential. Several studies have addressed the efficacy of GHRH as an alternative therapy in GHD. It appears that GHRH can be equally effective, whether given in a pulsatile manner or as discrete injections several times a day; i.e. the total dose may be more crucial than how it is given. While there are several issues that must be addressed before an optimal GHRH regimen can be devised, the available data would suggest that GHRH may become a safe, effective alternative to GH therapy in some patients with GHD.

Child↗
PubMed1986

Identification and characterization of a vasopressin isoreceptor in porcine seminal vesicles.

Neurohypophysial hormones stimulate the motility of tunica albuginea, epididymis, and vas deferens acting through oxytocin (OT) and V1 vasopressin receptors. To test the hypothesis that these hormones are involved also in the regulation of seminal vesicle physiology, we studied binding of [3H]OT and [3H] arginine vasopressin ([3H]AVP) to porcine seminal vesicle membranes. Neurohypophysial hormones bind to two different classes of sites. The first class shows low capacity (35 fmol per mg of protein) and a very high affinity (Kd less than 1 nM) for both the labeled ligands. The second class is characterized by a high capacity (2000 fmol per mg of protein) and a high affinity for AVP (Kd approximately equal to 2.5 nM), whereas OT has 160 times lower affinity. Lysine vasopressin and the V1 antagonist [1-deaminopenicillamine, 2-(O-methyl)tyrosine]Arg8-vasopressin compete with high affinity with [3H]AVP binding, whereas the V2 agonist [1-deamino,4-valine]D-Arg8-vasopressin (dVDAVP) is 110 times less potent than AVP. The OT agonist [Thr4,Gly7]OT and the OT antagonist [1(beta-mercapto-beta, beta-cyclopentamethylene propionic acid), 2-(O-ethyl)tyrosine, 8-ornithine]vasotocin failed to affect [3H]AVP binding. These findings seem to suggest that AVP interacts with the V1 vasopressin isoreceptor in porcine seminal vesicle membranes. However, AVP stimulates adenylate cyclase activity in a dose-dependent fashion with an EC50 of 14 nM, whereas OT or dVDAVP has no effect at 100 nM. Moreover, a well-characterized V1 vasopressin antagonist, [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid),2-(O-methyl)tyrosine]Arg8-vasopressin [d(CH2)5Tyr(Me)AVP], competes with [3H]AVP binding with an IC50 of 0.17 microM. These pharmacological properties are distinct from the previously described V1 and V2 vasopressin receptors and indicate the presence of a new class of AVP receptors. Although this vasopressin isoreceptor shares some pharmacological characteristics with the V1 (pressor) isoreceptor, it has low affinity for the V1 antagonist d(CH2)5-Tyr(Me)AVP and is linked to the adenylate cyclase system. The extremely high density of AVP receptors in porcine seminal vesicles (2 pmol per mg of protein) is comparable to the density of V2 vasopressin receptors in porcine renal medulla, suggesting a physiological role for vasopressin in the seminal vesicle.

Adenylyl Cyclases↗
PubMed1986

Growth hormone (GH) responses to GH-releasing hormone during pubertal development in normal boys and girls: comparison to idiopathic short stature and GH deficiency.

The normal ranges for GH responses to GH-releasing hormone (GHRH) have previously been defined for adult men and women. To determine whether the GHRH responses of normal children differ from those of adults and whether children with GH deficiency (GHD) and children who are growing below the first percentile but are otherwise normal (ISS) have GH responses comparable to those of normal children, we studied 90 normal children, 46 girls and 44 boys, with heights between the 10th and 95th percentiles for age, at different pubertal stages. Their responses were compared to those of 24 children with ISS and 32 children with GHD and to values previously measured in young adult men and women. Girls were grouped by Tanner breast stages and boys by testicular volumes. Plasma somatomedin-C, estradiol or testosterone, and bone age were measured in all children. All received a 1 microgram/kg iv bolus dose of GHRH-(1-44)NH2, and GH responses were measured during a 2-h sampling period. Incremental serum GH responses in girls did not change throughout pubertal development and were similar to those of adult women. The responses in boys at midpuberty were somewhat lower (P less than 0.05) than those in either prepubertal boys or adult men. ISS children had mean GH responses [23 +/- 4 (+/- SE) ng/ml] similar to those of normal children. GHD children had significantly lower mean GH responses (11 +/- 3.7 ng/ml) than normal prepubertal children (35 +/- 4.0 ng/ml; P less than 0.01), but the responses of 17 of the 32 GHD children overlapped with the normal range. GH responses to GHRH were not correlated with bone age, weight, height, SmC levels, or estradiol or testosterone concentrations. These results indicate that GH responses to GHRH testing are relatively constant throughout puberty and young adulthood, that ISS children respond normally to GHRH, and that the GHRH test is not a reliable discriminator between individual normal and GHD children.

Adolescent↗
PubMed1986

Effects of ketoconazole on rat ovarian steroidogenic enzymatic activities.

Ketoconazole (K) is an antifungal imidazole derivative which is a potent inhibitor of steroid biosynthesis in rodents and humans. To study the effect of K on rat ovarian steroidogenesis we measured the activities of five ovarian microsomal steroidogenic enzymes in K-treated rats and controls. Thirty hypophysectomized, gonadotropin-treated female adult rats were given either 2 mg K or water every 12 hours by mouth during 5 days. Mean ovarian weight was similar in both groups of animals. The K-treated group had an estradiol (E) serum concentration of 176 +/- 48 pg/ml whereas it was 278 +/- 56 pg/ml in the control group (NS). The K-treated animals had decreased activities of the 17,20-desmolase, 17-ketosteroid-reductase and aromatase enzymes. The 3 beta hydroxysteroid-dehydrogenase and 17-hydroxylase activities were similar in both groups. We conclude that K directly inhibits the activities of the 17,20-desmolase, 17-ketosteroid-reductase and aromatase enzymes in the rat ovary.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

Effects of ketoconazole on rat testicular steroidogenic enzymatic activities.

Ketoconazole (K) is an antifungal imidazole derivative which has been shown to be a potent inhibitor of testosterone (T) biosynthesis in rodents and humans. To study the effect of K on rat testicular steroidogenesis we measured the activities of five testicular microsomal steroidogenic enzymes in K-treated rats and controls. Thirty male adult rats were given either 2 mg K or water every 12 hours by mouth during 5 days. Mean testicular weight was similar in both groups of animals. The K-treated group had a T serum concentration of 83 +/- 14 ng/dL whereas it was 94 +/- 16 ng/dL in the control group (NS). The K-treated animals had decreased activities of the 3 beta-hydroxysteroid dehydrogenase (830 +/- 48 vs 2,245 +/- 109 pmol/mg protein/min, P less than 0.001), 17-hydroxylase (243 +/- 5 vs 676 +/- 17 pmol/mg protein/min, P less than 0.001), 17-ketosteroid reductase (31 +/- 2 vs 169 +/- 7 pmol/mg protein/min, P less than 0.001), and aromatase enzymes (92 +/- 6 vs 123 +/- 7 pmol/mg protein/min, P less than 0.01). The 17,20-desmolase activity was similar in both groups of animals (210 +/- 4 vs 171 +/- 18 pmol/mg protein/min). We conclude that K given orally to rats inhibits the activity of several testicular steroidogenic enzymes.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

Direct effect of the luteinizing hormone releasing hormone analog D-Trp6-Pro9-Net-LHRH on rat ovarian steroidogenesis.

The luteinizing hormone releasing hormone analog D-Trp6-Pro9-Net-LHRH (LHRHa) inhibits rat ovarian estradiol secretion. To determine whether LHRHa decreases serum estradiol concentrations solely by inhibiting gonadotropin secretion or, in addition, by influencing directly ovarian estradiol biosynthesis, we examined the effects of LHRHa on the activities of 5 key ovarian steroidogenic enzymes. Fifty hypophysectomized, gonadotropin-treated rats were given either LHRHa (1 microgram/day) or saline sc during 7 days. The LHRHa treated animals exhibited a significant decrease in serum estradiol when compared with the control group (461 +/- 30 vs 31 +/- 5 pg/ml, mean +/- SE, P less than 0.001). The changes in estradiol concentration were associated with decreases in ovarian weight (372 +/- 19 vs 185 +/- 11 mg, P less than 0.001) and in the microsomal enzyme activities of 3 beta-hydroxysteroid dehydrogenase (156 +/- 5 vs 53 +/- 4 nmol/mg prot/min, P less than 0.001), 17 hydroxylase (4.7 +/- 0.8 vs 3.7 +/- 0.7 nmol/mg prot/min, P less than 0.002), 17,20 desmolase (279 +/- 14 vs 50 +/- 7 pmol/mg prot/min, P less than 0.001), 17 keto-steroid reductase (132 +/- 11 vs 6 +/- 1 nmol/mg prot/min, P less than 0.001), and aromatase (19 +/- 1.5 vs 0.9 +/- 0.1 nmol/mg prot/min, P less than 0.001) in LHRHa treated animals. These findings indicate that LHRHa can inhibit directly rat ovarian estradiol biosynthesis.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

Effects of pulsatile administration of growth hormone (GH)-releasing hormone on short term linear growth in children with GH deficiency.

To assess the efficacy of GH-releasing hormone (GHRH) in the treatment of GH deficiency, we measured the effects of pulsatile iv GHRH administration on GH secretion, plasma levels of somatomedin-C (SmC), and short term linear growth (as determined by lower leg measurements) in seven GH-deficient children in a placebo-controlled study. Either GHRH, at a dose of 1 microgram/kg (seven patients), or 0.9% saline (NS; four of these patients) was given iv every 3 h for 9-12 days; all patients also received GH for a similar period. Lower leg length was measured every 3 weeks before and after each treatment. GHRH was more effective than placebo in accelerating linear growth (P less than 0.05). The responses, however, were heterogeneous; four of the children responded with accelerated growth, and three did not. Two of the children who failed to grow had no increase in plasma GH or SmC during GHRH administration, and one had an attenuated GH response. The four children who grew had induction of pulsatile GH secretion [mean peak GH, 10.4 +/- 1.3 (+/- SEM) ng/ml after GHRH vs. 1.5 +/- 0.5 ng/ml after NS; P less than 0.05] and elevation in SmC levels (maximum, 0.5 +/- 0.1 U/ml during GHRH vs. 0.19 +/- 0.05 during NS; P less than 0.01). The lower leg growth velocity during GHRH treatment (2.8 +/- 0.2 mm/3 weeks) was greater than their own basal rate (0.6 +/- 0.2 mm/3 weeks; P less than 0.01) or their growth during placebo treatment (0.4 +/- 0.2 mm/3 weeks; P less than 0.01). Thus, repeated administration of GHRH stimulated increases in GH and SmC in some but not all GH-deficient children. The growth response appears to be related to the magnitude of the GHRH-stimulated rise in GH levels. GHRH increases short term linear growth in some children with GH deficiency and holds promise as an alternative to GH as a form of therapy in these patients.

Adolescent↗
PubMedDate not supplied

Glucocorticoidlike activity of megestrol. A summary of Food and Drug Administration experience and a review of the literature.

Sporadic single case reports linking glucocorticoidlike activity to megestrol acetate have been reported in the literature. These findings have important implications for patient care. Adverse drug experience reports to the US Food and Drug Administration from 1984 through 1996 and a MEDLINE search of the literature from 1984 through 1996 provided the case reports. Five cases of Cushing syndrome, 12 cases of new-onset diabetes, and 16 cases of adrenal insufficiency were identified in association with megestrol therapy. Twelve cases in which preexisting diabetes was exacerbated and 17 cases of possible adrenal insufficiency were identified. Therapy with megestrol can result in clinical manifestations of glucocorticoidlike activity, including Cushing syndrome, diabetes, and adrenal insufficiency. Clinicians need to be aware of this association as these complications can be life-threatening if not recognized.

Adrenal Insufficiency↗