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S Handwerger

Publications and source records attributed to S Handwerger.

At least 145 records · Page 8Linked to original sources

Failure of acute changes in prolactin to affect DHEA-S secretion in the human.

To investigate whether acute changes in prolactin secretion affect adrenal androgen secretion, serum prolactin and dehydroepiandrosterone sulfate (DHEA-S) concentrations were determined in seven normal women following the administration of chlorpromazine and L-dopa. The changes in plasma prolactin and DHEA-S concentrations over a four-hour period were compared to those in control experiments in which four of the women received placebo alone. Following the administration of chlorpromazine, plasma prolactin concentrations increased four-fold above pretreatment concentrations, reaching a maximum at 120 minutes. Following L-dopa, plasma prolactin concentrations decreased by greater than 50%, with the nadir noted within 90 minutes. Despite these acute changes in prolactin secretion, plasma DHEA-S concentrations remained unchanged. These results, therefore, strongly suggest that acute changes in prolactin secretion have no affect on adrenal androgen secretion.

Adult↗

Demonstration of intracellular and secreted forms of large human chorionic gonadotrophin alpha subunit in cultures of normal placental tissue.

Free human chorionic gonadotrophin (hCG) alpha-subunit in tissue extracts and incubation media of normal placentae before and after four days of culture was investigated by Sephadex G-100 chromatography. Prior to incubation, tissue extracts of first-trimester and term placentae contained a large form and a small form of alpha-subunit relative to a reference urinary hCG alpha-subunit preparation. The large alpha-subunit comprised 30.6 +/- 1.4 per cent s.e.m. and the small alpha-subunit, 66.9 +/- 4.1 per cent of total intracellular alpha-subunit. After 96 h of incubation, the large alpha-subunit comprised 77.6 +/- 9.8 per cent of the total intracellular alpha-subunit, and the small 21.0 +/- 8.1 per cent. The incubation medium contained a single form of alpha-subunit which eluted with a larger apparent molecular weight than the urinary hCG alpha-subunit. Following neuraminidase treatment, the large alpha-subunit from tissue extracts eluted as a smaller molecule in the position of the urinary hCG alpha reference. A change in Ve/Vo of the small alpha-subunit was not detected. Identical neuraminidase treatment of the large alpha-subunit from incubation medium resulted in an increase in the Ve/Vo, but the large alpha-subunit continued to elute from Sephadex G-100 before the urinary hCG alpha-subunit. However, large alpha-subunit from culture medium did elute in the position of urinary hCG alpha following mild acid hydrolysis. These studies demonstrate that a large form of alpha-subunit is present in first-trimester and term placental tissue both before and after incubation in vitro and that the large form of alpha-subunit is secreted by the normal placenta. The differential effects of neuraminidase treatment on the intra- and extracellular forms of large alpha-subunit coupled with our findings from acid hydrolysis of the extracellular form suggest that alpha-subunit secreted into the culture medium may contain additional carbohydrate residues not present on the intracellular form.

Choriocarcinoma↗

Influence of osmolality and ionic environment on the secretion of prolactin by human decidua in vitro.

The effects of extracellular osmolality and ions on the secretion of prolactin were examined in human decidual explants incubated for 4 h in modified Krebs-Ringer buffer. Explants incubated in media made hypersomotic (280-336 mosM/kg) with sodium, lithium or mannitol or in media made hypo-osmotic (280-224 mosM/kg) by decreasing the sodium concentration secreted the same amount of prolactin as explants incubated in control medium (280 mosM/kg). Explants incubated in calcium-deficient medium secreted 64 +/- 8% (P less than or equal to 0.001) less prolactin than controls (1.65 mmol Ca2+/1). Secretion was restored to control values by the addition of calcium (0.33 mmol/l) or barium (0.5, 1.0 or 2.0 mmol/l) to the medium. Prolactin secretion was unaffected by higher than control extracellular calcium concentrations, calcium ionophore A23187 (10-6, 10-9 mol/l) or lanthanum (0.5, 1.0 or 2.0 mmol/1). Changes in extracellular magnesium (0-20 mmol/l), potassium (0-55 mmol/l) or bicarbonate (0-32 mmol/l) had no effect on prolactin secretion. These results indicate that marked changes in extracellular osmolality and concentrations of sodium, magnesium and bicarbonate have no effects on decidual prolactin secretion. Calcium, however, is essential for the basal secretion of decidual prolactin.

Calcium↗

Development of a heterologous radioimmunoassay for somatomedin C in sheep blood.

A heterologous radioimmunoassay for the measurement of somatomedin C in sheep serum has been developed using purified 125I-labelled human somatomedin C and an antiserum to human somatomedin C. It was observed that the GH dependence of somatomedin C could not be verified when unprocessed sheep sera were assayed, because of interference by somatomedin binding proteins. After incubation of samples at pH 3.8, however, concentrations of somatomedin C mirrored GH status. Assays results from sera after prolonged exposure to acid agreed with results from which had undergone acidification and gel chromatography. Using the methods developed in this study, 12 sera from normal sheep had a mean concentration of somatomedin C of 2.35 +/- 0.27 (S.E.M.) units/ml while nine sera from hypophysectomized sheep contained 0.45 +/- 0.04 units/ml (P less than 0.001), and one serum from a ewe with a prolonged GH excess associated with a pituitary tumour had a value of 6.9 units/ml. The radioimmunoassay resulting from these studies should provide a tool for investigation of the physiological control of somatomedin C in sheep.

Animals↗

Human placental lactogen release in vitro: paradoxical effects of calcium.

To study the effects of calcium on the release of human placental lactogen (hPL), placental explants were exposed to media containing lower or higher concentrations of calcium than normally available to the placenta. Explants exposed for 2 h to calcium-poor medium or medium containing either 2 mM EDTA or 2 mM EGTA released 160, 248, and 253% more hPL, respectively, than control explants. In contrast, explants exposed to medium containing higher than normal calcium concentrations released the same amounts of hPL as the control explants. At lower than normal extracellular calcium concentrations, the increased hPL release was inversely proportional to the calcium concentration. The increased release in calcium-poor medium was inhibited by subsequent exposure of the explants to medium containing calcium and was prevented by either barium or magnesium. Changes in barium or magnesium concentrations, however, had no effects on hPL release in the presence of normal extracellular calcium concentrations. Methoxyverapamil (D 600), an inhibitor of calcium flux, stimulated hPL release. Because low extracellular calcium and methoxyverapamil both inhibit calcium influx, these experiments suggest that calcium influx inhibits hPL release. The role of calcium in the regulation of hPL release therefore appears to be different from that reported in other release systems.

Barium↗

Inhibition of the synthesis and secretion of decidual prolactin by arachidonic acid.

Human decidual explants exposed for 4 h to 150 microM arachidonic acid synthesized and secreted 30.4% (P less than 0.001) and 36.4% (P less than 0.001) less 35S-PRL, respectively, than control explants. Over a 5-h period, the inhibition of PRL secretion was directly proportional to the arachidonic acid concentration at concentrations between 30 and 300 microM (r = 0.91; P less than 0.001). Phospholipase A2 at concentrations of 0.11 and 11.1 U/ml, also inhibited PRL secretion by 46.2 +/- 2.4% (P less than 0.001) and 63.9 +/- 1.4% (P less than 0.001), respectively. Likewise, the fatty acid precursors of arachidonic acid, i.e. linoleic, gamma-linolenic, and dihomo-gamma-linolenic acids, inhibited PRL secretion, but palmitic, oleic, and 11,14,17-icosatrienoic acids and the detergents deoxycholic acid and Triton X-100 had no effects, even at concentrations as high as 300 microM. In contrast, prostaglandins E1, E2, and F2 alpha (3 X 10(-5)-10(12) M each) had no effects on PRL secretion, and the prostaglandin synthetase (cyclooxygenase) inhibitors indomethacin (5 and 25 micrograms/ml) and flufenamic acid (5 micrograms/ml) had no effects on either basal PRL secretion or the inhibitory action of arachidonic acid. These results suggest that arachidonic acid may be involved in the regulation of the synthesis and secretion of decidual PRL. The effect of arachidonic acid, however, does not appear to be mediated by a cyclooxygenase product of arachidonic metabolism.

Arachidonic Acid↗

Stimulation by ornithine of ovine placental lactogen secretion.

Arginine is a potent stimulus to the secretion of placental lactogen (PL) as well as GH and prolactin in sheep. To determine whether other amino acids of the urea cycle also affect PL secretion, ornithine (25 g) and citrulline (20 g) were infused intravenously into four pregnant ewes over a period of 0.5 h. In eight experiments, ornithine stimulated PL secretion by 124 +/- 25 (S.E.M.) % with the initial increase occurring by 1 h after the start of each infusion. Plasma GH concentrations increased from 3.4 +/- 1.1 to 24.5 +/- 5.9 ng/ml and plasma prolactin concentrations increased from 58.8 +/- 12.8 to 310.7 +/- 88.4 ng/ml. Citrulline, on the other hand, had no consistent effect on PL secretion. Plasma GH concentrations following the infusion of citrulline, however, increased by 15-20 ng/ml in two of four experiments and plasma prolactin concentrations decreased by 73.2 +/- 3.2% in all four experiments. The results indicate that ornithine is also a potent stimulus to the secretion of PL, GH and prolactin and suggest that arginine-induced PL secretion may result from the conversion of arginine to ornithine.

Animals↗

The relationship between breed and litter size in sheep and maternal serum concentrations of placental lactogen, estradiol and progesterone.

Milk production in sheep is known to be affected by breed and litter size. To investigate a possible hormonal basis for such effects, we measured maternal serum concentrations of placental lactogen, estradiol and progesterone during late gestation in sheep of several breeds and ages. Circulating concentrations of placental lactogen were directly related to litter size in all breeds, with the greatest concentrations being observed in Finnish Landrace ewes bearing three lambs. Among monotocous animals, no significant breed differences were observed, but ewe lambs bearing crossbred fetuses had higher placental lactogen concentrations than ewes of the same breed carrying purebred offspring. Placental lactogen concentrations were similar in all animals bearing twins, except for Corriedale ewes, which had the lowest concentrations. Serum estradiol concentrations 2 to 5 weeks prepartum did not differ between ewes of different breeds or ewes with different litter sizes. Progesterone, like placental lactogen, was related to litter size and, presumably placental mass. The relationship between litter size and placental lactogen concentrations, together with the absence of difference in estradiol secretion, suggests that differences in production of the lactogenic hormone may contribute to the superior lactational performance that has been reported for ewes which bear multiple offspring.

Animals↗

Failure of bromocriptine, dopamine, and thyrotropin-releasing hormone to affect prolactin secretion by human decidual tissue in vitro.

To determine whether the secretion of PRL by human decidual tissue in vitro is influenced by factors which inhibit or stimulate pituitary PRL secretion, explants of decidual tissue were incubated in media containing bromocriptine, dopamine, or TRH at concentrations known to affect pituitary PRL secretion in vitro. The quantities of PRL secreted by the explants exposed to these factors were compared with amounts secreted by explants incubated in control medium. Bromocriptine in concentrations ranging from 1.5 x 10(-10) to 1.5 x 10(-7) M did not inhibit PRL secretion over a 3-day period and dopamine in concentrations ranging from 5 x 10(-5)-10(-9) M did not inhibit PRL secretion over a 4-h period. TRH in concentrations ranging from 10(-9)-10(-3) M did not stimulate PRL secretion. These results suggest that the mechanism of PRL secretion by decidual tissue in vitro is different, at least in part, from the mechanism of pituitary PRL secretion.

Bromocriptine↗

Synthesis of prolactin by human decidua in vitro.

To determine whether human decidua and/or chorion synthesizes and secretes prolactin, explants of decidua obtained at Caesarian section and explants of chorion from the membranes separating dizygotic twins were cultured for periods of up to 6 days. The decidual explants released 366 +/- 37 ng prolactin/100 mg tissue (mean +/- S.D.) during each day in culture and incorporated 3H-labelled amino acids into immunoprecipitable prolactin. In the radioimmunoassay for prolactin, serial dilutions of incubation medium displaced 125I-labelled prolactin parallel to the displacement by pituitary prolactin and the prolactin in the medium eluted from Sephadex G-150 in a position indentical to that of pituitary prolactin. Chorionic explants released prolactin into the incubation medium during day 1 of culture only and did not incorporate 3H-labelled amino acids into prolactin. These results demonstrate that prolactin is synthesized by the decidua and not by the chorion and suggest that the decidua is the source of prolactin in amniotic fluid.

Amino Acids↗

Prolactin synthesis by human chorion-decidual tissue: a possible source of prolactin in the amniotic fluid.

Explants of human chorion-decidual tissue obtained at delivery from normal, full-term pregnancies synthesize and secrete prolactin. This hormone is indistinguishable from pituitary prolactin by chromatographic, electrophoretic, immunologic, and receptor assay techniques. These results suggest that chorion-decidua may be the source of the large quantities of prolactin in amniotic fluid.

Amnion↗

Stimulation of ovine placental lactogen secretion by arginine infusion.

Arginine has been demonstrated to be a potent stimulus to GH and PRL secretion. To determine the effect of arginine on plasma ovine placental lactogen (oPL) concentrations, arginine (50 g in 350 ml distilled water, pH 7.4) or hypertonic saline of identical volume, osmolality, and pH was infused iv over a 30-min period into nine pregnant ewes, and blood samples from chronic indwelling venous catheters were obtained at frequent intervals before and for 8 h after the infusions. After the infusion of hypertonic saline, plasma oPL concentrations (measured by homologous RIA) decreased 20--50% over 1--2 h and then returned to baseline concentrations. After the infusion of arginine, plasma oPL concentrations also decreased by 20--50% for 1--2 h. However, 2--3 h after the infusion, plasma oPL concentrations in creased 79--115% (delta = 204--700 ng/ml) over preinfusion concentrations in seven ewes and 454% (2930 ng/ml) and 1142% (2042 ng/ml) in two ewes and remained elevated for the remainder of the 8-h interval. When the amount of arginine infused was reduced from 50 to 25 g, an increase in plasma oPL concentrations occurred in only one of five ewes. Plasma oPL concentrations increased by 8--58% after infusions of 50 g alanine or glycine but did not increase after 50 g glutamic acid. The delayed oPL response to arginine suggests that the increase in plasma oPL concentrations is not caused directly by arginine but rather by changes in the synthesis, secretion, and/or degradation of oPL induced indirectly by arginine.

Animals↗