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W H Pearlman

Publications and source records attributed to W H Pearlman.

At least 19 recordsLinked to original sources
PubMed1986

In vitro metabolism of adrenocortical hormones by mammary glands of lactating rats. A comparative study.

A comparative study was made of the metabolism of tritium-labeled corticosterone, cortisol and aldosterone on incubation with minced mammary glands of lactating rats. The yield of total nonpolar (acylated) radiometabolites was highest for [3H]corticosterone, lowest for [3H]cortisol and intermediate for [3H]aldosterone. Unlike [3H]corticosterone, [3H]aldosterone yielded two 21-acyl derivatives (Metabolites I and II) in comparable amounts. Metabolite I (39%) was identified as [3H]aldosterone 21-oleate by isotope dilution analysis. Metabolite II (54%) could not be identified: it is intermediate in polarity between corticosterone 21-oleate and the less polar, corticosterone 21-stearate, and is distinctly less polar than the 21-palmityl, linoleoyl (and presumably also less polar than the arachidonyl) derivatives of aldosterone. The [3H]cortisol metabolites were not further investigated.

Acetylation↗
PubMed1986

Adrenocortical hormones and lactation: metabolism of 3H-corticosterone and 3H-aldosterone by rat mammary gland minces and by the nuclear fraction of the homogenates.

3H-Corticosterone undergoes extensive metabolism on incubation with mammary acini and minced mammary glands from lactating rats; 3H-corticosterone-21-oleate was the major radiometabolite formed. In a similar study with 3H-aldosterone, 3H-aldosterone-21-oleate was one of the two major radiometabolites formed. In the present study, an enzyme system highly active in the biosynthesis of 21-acyl-3H-corticosterone was demonstrated to be present chiefly in the nuclear fraction of mammary gland homogenates. The enzyme system comprises: a fatty acid thiokinase (or fatty acyl-CoA synthetase); a fatty acyl transferase. The methods entailed incubation of 3H-corticosterone with the nuclear fraction in the presence and absence of: the cofactors, CoA, ATP, and Mg2+; oleoyl-CoA and other fatty acyl-CoA donors. The results of the present investigation support the view that the major cellular site for the acylation of adrenocortical hormones is the nucleus. It has been suggested that the acylation serves to modulate the biological action of the hormones on the mammary glands by interaction with the glucocorticoid receptor.

Acyl Coenzyme A↗
PubMed1985

In vitro metabolism of [3H] corticosterone by mammary glands from lactating rats. Isolation and identification of 21-acyl[3H]corticosterone.

[3H] Corticosterone undergoes extensive 21-acylation on incubation with minced mammary glands from lactating rats. A purified 21-acyl [3H] corticosterone fraction was obtained by subjecting extracts of the incubated tissues to Sephadex LH-20 column chromatography followed by partitioning between n-heptane/methanol. The methanol extracts were chromatographed consecutively on columns of silica gel and C18-silanized (reverse-phase) silica gel. The radioactive product was methoximated and re-chromatographed on the reverse-phase column. Mass spectral analysis of the 21-acyl [3H] corticosterone 3,20-dimethoxime and synthetic corticosterone 21-oleate 3,20-dimethoxime suggested identity. Confirmation of the precise nature of the 21-acyl moiety was obtained by isotope dilution analysis of the underivatized radiometabolite with corticosterone 21-oleate. The composition of the 21-acyl [3H] corticosterone fraction (i.e. before extensive purification) was ascertained by isotope dilution analysis with various corticosterone esters. It appears that [3H] corticosterone 21-oleate is a major component of this fraction, representing 80% of the radioactivity; [3H] corticosterone 21-linoleate is a minor component, i.e. 8.6%. [3H] Corticosterone 21-palmitate, [3H] corticosterone 21-arachidonate, and [3H] corticosterone 21-stearate, if indeed present, constitute considerably less than 14, 6, and 2%, respectively, of the radiometabolite fraction. It is suggested that bioacylation of corticosterone serves to modulate the biological action of the glucocorticoid hormone on the mammary glands during lactation.

Animals↗
PubMed1983

Glucocorticoids and lactation. In vitro metabolism of glucocorticoids by rat mammary glands.

In view of: 1. the extensive in vitro 21-acylation of [3H]corticosterone by rat mammary glands, especially during lactation; 2. the accumulation of 21-acyl [3H]corticosterone as the predominant form of the hormone in the alveolar nuclear fraction with which it is strongly associated; 3. the results of a systematic study of the influence of acylation per se of corticosterone and dexamethasone on their binding affinities for specific glucocorticoid-binding proteins; and 4. the extensive metabolic acylation, similarly, of adrenocortical hormones other than corticosterone, it is suggested that the acylation of glucocorticoid by the mammary gland may serve to modulate the biological action of the hormone on this target organ, and indirectly influence the flow of glucocorticoid from plasma to milk.

Acylation↗
PubMed1981

The levels of corticosterone-binding proteins in rat milk and coincidental serum, and the dissociation rates of the corticosterone.protein complexes.

The corticosterone-binding protein present in rat whey was further characterized by determining, with the aid of a dextran-coated charcoal procedure, the apparent rate of dissociation of the corticosterone.protein complex. The half-time values for the dissociation of the corticosterone.protein complexes in rat whey and serum were compared and found to be identical, i.e. 23 min at 0 C, when the measurements were made over a period of 40 min. The possible presence in small amounts of a corticosterone.protein complex in whey with the much slower dissociation rate characteristic of mammary glucocorticoid receptor could not be detected even when the dissociation was followed over a much longer period. The charcoal adsorption method also provided independent estimates of the molar concentrations of the corticosterone-binding proteins in rat serum and whey. The mean concentration of corticosterone-binding protein in whey was found to be 15% of that in coincidental serum during early lactation. The serum levels of corticosterone-binding protein decline markedly at parturition and then rise from day 2 to day 6 of lactation in rats with small litters. The results of this and a previous study suggest that the corticosterone-binding protein in whey is probably derived from that in serum. The mode of transport of the corticosterone-binding protein from the bloodstream across the mammary epithelium into milk as well as the concentrations of the corticosterone-binding proteins in serum and whey may be factors influencing the uptake of the glucocorticoid by its target cells.

Animals↗
PubMed1981

In-vitro uptake and metabolism of [3H] corticosterone by mammary glands from pregnant, lactating, and post-lactational rats and by parametrial adipose tissue from lactating rats.

The study was designed to determine the influence of the physiological state on the in-vitro uptake and metabolism of glucocorticoid hormone by the mammary gland. [3H] Corticosterone was accordingly incubated with minced mammary glands from pregnant, lactating and post-lactational rats. The total uptake of [3H] corticosteroid was obtained from the concentration of radioactivity by the tissue and the specific activity of the steroid substrate. The extent of 21-acylation was determined as the percentage of the radioactivity in the chromatographed tissue extracts attributable to 21-acyl-[3H] corticosterone. The results indicated that the uptake of [3H] corticosteroid increased with advancing pregnancy, attained a high plateau level during lactation, and steadily declined during the post-lactational period. The extent of 21-acylation of [3H] corticosterone varied from 10 to 40%, fluctuating widely in all physiological states, particularly during the post-lactational period. It was inferred that the stromal elements, presumably the adipocytes, of the mammary gland can also acylate the corticosteroid hormone, a view which gained experimental support from similar studies with minced parametrial adipose tissue from lactating rats.

Acylation↗
PubMed1979

Electrolytes of breast-cyst fluid.

We constructed an electrolyte balance sheet for 11 individual specimens and two pooled specimens of breast-cyst fluid. Na+ and K+ ranged in concentrations from those representative of extracellular fluids (147 and 9 mmol/L, respectively) to those of intracellular fluid or a high K+ secretion (23 and 168 mmol/L, respectively). Cl- concentrations ranged from 9 to 98 mmol/L (mean, 31), bicarbonate concentrations from 0 to 34 mmol/L (mean, 16). Ca2+ concentrations did not exceed 2.1 mmol/L. Total protein ranged from 14.7 to 35.8 gL. Fluid osmolality ranged from 249 to 300 mOsm/kg of water (mean, 280). The difference between measured cations and anions indicates an "anion gap" of 140 mmol/L, which must be carried by 46 mOsm/kg of water. We suggest that tricarboxylic acids of the Krebs cycle may account for the missing trivalent anions.

Bicarbonates↗
PubMed1977

Maternal and fetal serum levels of total cortisol and cortisone, unbound cortisol, and corticosteroid-binding globulin in vaginal delivery and cesarean section.

The levels of corticosteroid-binding globulin (CBG, transcortin), total cortisol, and unbound cortisol were measured in maternal and fetal serum at the time of cesarean section or vaginal delivery. While the total cortisol levels in maternal serum do not differ significantly in vaginal delivery as compared to cesarean section, cord serum cortisol levels are significantly higher after vaginal delivery. There are no differences associated with the route of delivery between the mean levels of CBG in cord and maternal blood. However, after the vaginal delivery the unbound cortisol level in maternal serum is more than twice as high as that at cesarean section and in cord serum it is seven times as high. These changes reflect changes in total cortisol and may represent a prelabor surge of fetal cortisol production, or a stress response associated with labor, or a combination of both.

Cesarean Section↗
PubMed1976

Corticosteroid-binding proteins in human colostrum and milk and rat milk.

A corticosteroid-binding protein was detected in the whey of human colostrum and milk which resembles serum corticosteroid-binding globulin in certain respects: the equilibrium association constants for cortisol and progesterone binding and the apparent molecular size, as determined by Sephadex G-200 chromatography, were similar, and cortisol andd progesterone competed strongly for binding to the same site in each instance. Dexamethasone-binding activity could not be detected. The concentration of corticosteroid-binding protein in the colostrum obtained before parturition is about 0.1 muM; the concentration declines rapidly after parturition to about 0.01 muM. A corticosteroid-binding protein was found, also, in the whey of mature rat milk at levels of about 0.3 muM. This protein resembles rat serum corticosteroid-binding globulin: the equilibrium association constants for cortisol, corticosterone, and progesterone binding, and the apparent molecular size, as determined by Sephadex G-200 chromatography, were similar; the elution behavior of the respective proteins on anion exchange chromatography with DEAE-Sephadex A-50 was similar, also. Identity of the corticosteroid-binding proteins in whey with corticosteroid-binding globulin in serum is not presumed, however. Rat and human whey exhibited very little testosterone- or 17 beta-estradiol-binding activity. It is suggested the corticosteroid-binding proteins may play a significant physiological role in regulating the concentration of the bound and unbound forms of progesterone and cortisol in the fluids bathing the epithelial cells lining the mammary ducts and acini.

Adrenal Cortex Hormones↗