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Biomedical subjects

R T Chatterton

Publications and source records attributed to R T Chatterton.

At least 91 records · Page 5Linked to original sources
PubMed1981

Interaction of steroids with dexamethasone-binding receptor and corticosteroid-binding globulin in the mammary gland of the mouse in relation to lactation.

Dexamethasone (9 alpha-fluoro-11 beta, 17, 21-trihydroxy-16 alpha-methyl-pregna-1,4-diene-3,20-dione) binding by cytosolic components of mammary glands from pregnant and lactating mice was characterized and quantified. The unfilled receptor for mice was characterized and quantified. The unfilled receptor for dexamethasone lost binding activity rapidly by a process that was largely, but not completely, reversed by the addition of sulfhydryl reagents. The quantity of dexamethasone receptors increased 4-fold during the last 8 days of pregnancy. The apparent binding affinity (Ka) calculated from Scatchard plots was maximal at parturition (1.5 x 10(8)M-1), but declined gradually as lactation progressed. A mixture of cytosols from pregnancy and lactation gave a linear Scatchard plot, with a Ka that was the mean of the Ka values obtained in the separate cytosols. The decreased Ka in lactating mice was not due to a different class of receptors, but may be attributed to the increased levels of endogenous free steroids in the cytosol. Some differences, however, were noted between the sedimentation properties of the dexamethasone-receptor complexes in cytosols of pregnant and lactating mice. In addition to the dexamethasone-binding activity, a binding substance identical to corticosteroid-binding globulin (CBG) was identified in the cytosol fraction of mammary glands. CBG in glands of lactating mice was saturated with endogenous steroids, but that in pregnant mice was only 8% saturated. The presence of high concentrations of unsaturated CBG in the vicinity of the parenchymal cells would decrease the availability of corticosteroids to the receptors in pregnancy and may be an important mechanism for the control of the initiation of milk secretion.

Animals↗
PubMed1979

Ultrastructural alterations in mammary glands of pregnant rats after ovariectomy and hysterectomy: effect of adrenal steroids and prolactin.

Pregnant rats were subjected to oophorectomy and hysterectomy (O-H) on the seventeenth day of pregnancy, a time when serum levels of prolactin, estrogen, and corticosterone are not substantially greater than the respective levels in nonpregnant rats. At 32 hours after O-H, serum prolactin and corticosterone both rose more than threefold, and lactose appeared in the mammary glands. Biopsies of mammary tissue obtained at 8 hour intervals after O-H showed a progressive secretory response over 16 hours, similar to that previously shown to occur within a period of about 4 hours on the last day of pregnancy. Suppression of serum prolactin by ergocriptine administration and adrenalectomy 24 hours before O-H each prevented the secretory response. However, some differences in the effects of deprivation of the two types of hormones were evident. After cortisol acetate administration at O-H, mammary tissue responded rapidly despite adrenalectomy 24 hours earlier. It is concluded that simple withdrawal of progesterone is not sufficient to initiate lactation in the pregnant rat; glucocorticoids must be present continuously during progesterone withdrawal, and prolactin elevation and other factors present at parturition may be required as well.

Animals↗
PubMed1979

Alterations in serum cortisol and its binding characteristics in anorexia nervosa.

The binding capacity and apparent binding affinity of corticosteroid-binding globulin (CBG) for cortisol was studied in 20 women hospitalized for anorexia nervosa. The binding capacity for cortisol, as determined kinetically at 0 C by the method of Scatchard, was similar in anorectic patients and control subjects, with mean values of 26.9 and 21.9 microgram/100 ml, respectively. The mean apparent affinity constant of CBG for cortisol was found to be significantly (P less than 0.01) lower (14.1 X 10(8) M-1) than that in control subjects (22.3 X 10(8) M-1) and was similar in blood drawn at 0830 and 2000 h. Mean morning total serum cortisol concentrations were higher in anorectic women (23.3 microgram/100 ml) than in controls (10.0 microgram/100 ml; P less than 0.001) and frequently exceeded the binding capacity of CBG. Diurnal variation was present. Mean serum 17 beta-estradiol levels were low (40.0 pg/ml) and serum progesterone was essentially absent, but mean serum testosterone levels were within the normal range. Eight patients who were retested after weight gain, when they were between 76--100% of ideal body weight, exhibited no significant changes in serum steroids or in the binding capacity or apparent affinity of CBG for cortisol.

Adolescent↗
PubMed1978

In vitro liver clearance of tritiated estradiol-17beta in the female rat after retrochiasmatic transection and ovariectomy.

It was reported in a previous study that serum estradiol-17beta (E2) was elevated in rats after retrochiasmatic transection (FC). Serum E2 was also higher in estradiol cypionate treated, ovariectomized (OVX) rats that had been subjected to FC than in those that had not. This suggested that increased secretion of E2 was not the only factor responsible for elevated serum E2 after FC. To ascertain the contribution of decreased metabolism of E2 to this response, liver tissue slices were incubated with 3H-estradiol-17beta, and the rates of 3H uptake and conversion to water-soluble conjugates were measured. The rate of uptake of 3H by the tissue was not indicative of the rate of conjugate formation. Livers of rats with high serum E2 exhibited lower rates of 3H uptake than those of rats with low serum E2. Even so, the formation of 3H conjugates was greater in liver of rats with high serum E2. As hypothesized, livers of rats with FC formed conjugates at a significantly lower rate than those of similarly treated rats without FC. Thus, FC of an intact rat leads to an increase in serum E2 by increasing the secretion of E2, and apparently also by decreasing the rate of E2 metabolism by the liver.

Animals↗
PubMed1978

Time-course relationships between serum LH, serum progesterone and urinary preganediol concentrations in normal women.

A specific and sensitive gas chromatographic method was used to investigate the concentration of pregnanediol glucuronide in urine in relation to the time of ovulation. Serum LH and progesterone concentrations in the same subjects were used as evidence for the occurrence of ovulation. The urinary concentration of pregnanediol glucuronide in 24-hour collections and in overnight specimens increased 2-fold or more from the day of the midcycle LH peak to the time of predicted ovulation (24-48 hour after the LH peak) in parallel with the rise in serum progesterone concentration.

Chromatography, Gas↗
PubMed1978

Vaginal transposition of the ovary in primates (Papio cynocephalus and Macaca arctoides).

Experimental data indicate that the time and mechanism of ovulation play a significant role in some cases of infertility and in a broad range of reproductive abnormalities. In order to establish a new experimental model for the study of these phenomena in primates, transposition of the ovary from the pelvis into the vaginal fornix was attempted in 2 species of monkeys: (a) Macaca Arctoides and (b) Papio Cynocephalus. Particularly in the latter species, ovarian relocation into the anterior and the posterior vaginal fornices proved feasible. Most ovaries continued functioning in their new location during the 2-5 months of the follow-up, despite macroscopic and microscopic evidence of infection. Post mortem examination of one of the experimental animals several years after the surgical procedure revealed the presence of an intact functioning ovary still in close contact with the vaginal fornix.

Animals↗
PubMed1976

Interaction of progesterone and adrenocorticoids in ultrastructural development of the mammary gland of the cat.

Comparative development of rough endoplasmic reticulum (RER) in mammary glands of rats was studied in relation to levels of progesterone and adrenocorticosteroids. The tranquilizer perphenazine was administered to stimulate secretion of prolactin; serum glucocorticoids also increased. When perphenazine was administered after ovulation, serum progesterone was increased 18-fold, but when treatment was begun on proestrus, ovulation was inhibited and serum progesterone increased only 4-fold. Concentrations of progesterone in the breast were approximately 10-fold greater than, but parallel to, serum concentrations. In ovulating rats the RER was poorly developed. In nonovulating rats extensive development of RER occurred. Cortisol acetate given to ovulating, perphenazine-treated rats did not alter levels of serum progesterone, but tissue progesterone was reduced by 50 per cent and development of RER approached that in nonovulating rats. The development of secretory capacity (formation of RER) in the breast appears to depend on the relation between stimulation by glucocorticoid and inhibition by progesterone.

Adrenal Cortex Hormones↗
PubMed1976

Effect of hypophysectomy on estrogen conjugation and on plasma and tissue concentrations of tritium after administration of 3H-estradiol-17beta.

Estradiol-17beta-6,7-3H was injected into ovariectomized (control) and ovariectomized, hypophysectomized (hypox) rats in order to study the binding of estradiol in the brain. Hypophysectomy resulted in a significant increase in the concentration of tritium in the hypothalamus, and preoptic area, as well as cortex, muscle, plasma and liver. However, since the liver was lighter in hypox rats, the total tritium content in the liver was unchanged from controls. Part of the weight reduction in the liver was due to a loss of stainable glycogen, which took place within 24 hours of hypox. The increase in circulating tritiated estradiol after hypox led us to investigate hepatic metabolism of estradiol. In vitro studies on liver slices from control and hypox rats demonstrated a significant reduction in the formation of conjugates of estrogen. Specifically, estradiol glucuronide and estrone sulfate formation were reduced in hypox rats and conversely the unmetabolized estradiol concentration was higher. Hypophysectomy for 24 hours results in a significant decrease in hepatic metabolism of estradiol-17beta.

Animals↗
PubMed1975

Differential responses of prelactating and lactating mammary gland to similar tissue concentrations of progesterone.

Serum and mammary tissue concentrations of progesterone and 20alpha-hydroxy-4-pregnen-3-one (20alpha-OHP) were measured by competitive protein-binding assays and gas-liquid chromatography, respectively, in pregnant and lactating rats. The concentration of progesterone in mammary tissue of pregnant rats closely paralleled the serum concentration, particularly when tissue concentration was expressed as ng/mg DNA. The variability in tissue progesterone on the last day of pregnancy was relatively great, but there was a good inverse relation between the appearance of lactose and the progesterone concentration. Serum progesterone levels declined to their lowest values at 1-3 days of lactation (10 plus or minus 1 ng/ml); the tissue concentration declined even more rapidly after parturition. The tissue 20alpha-OHP concentration, which was more closely related to serum progesterone among animals than to serum 20alpha-OHP, remained high after parturition suggesting that the presence of 20alpha-OHP has no effect on lactogenesis and that progesterone is decreased in the tissue by 20alpha-reduction. Following postpartum ovulation, serum progesterone increased to 74 plus or minus 6 ng/ml at 6-9 days of lactation; tissue progesterone also increased to levels found in rats pregnant 14-19 days, yet no change in lactose content of the glands of suckled rats occurred, and the biosynthetic capacity in terms of the RNA/DNA ratio increased. Serum 20alpha-OHP also rose, but the tissue concentration was unchanged, suggesting that saturating levels were present throughout pregnancy and lactation. Since no rapid increase in DNA was associated with lactogenesis, differentiation of nonsecretory parenchymal cells into daughter cells with the secretory capacity must occur earlier in pregnancy. Progesterone, therefore, must inhibit lactogenesis by preventing expression of the genetic potential of daughter cells. Once differentiation has been completed, however, the presence of progesterone in the tissue has no effect on the biosynthesis of milk constituents.

Animals↗
PubMed1975

Lactogenesis in the rat: an ultrastructural study of the initiation of the secretory process.

Three specimens were taken from mammary glands of rats killed on the 18th and 21st days of pregnancy and on the 1st day of lactation. Ultrastructural features of the tissue were compared among rats within and between the two stages of development. The similarity among specimens from the same rats made feasible a comparison of serial biopsies obtained every 4 hr, starting on the afternoon of the 21st day of pregnancy. From the 18th to the 21st days of pregnancy, a marked increase in the amount of rough endoplasmic reticulum occurred. The alveolar cells of rats killed on both days and in biopsies obtained at 17 and 13 hr before partuirtion contained abundant small lipid droplets and vacuoles containing many protein granules with little clear fluid (stasis vacuoles). Alveolar lumina were distended with secretion by 17 hr before parturition. Between 8 and 12 hr. before parturition, the accumulated protein and lipid were rapidly extruded from the alveolar cells despite evidence of continued biosynthesis. It is suggested that active transport processes are initiated independently of milk synthesis before parturition.

Animals↗
PubMed1975

Ovarian responses to perphenazine-induced prolactin secretion in the rats: Effect of ovulation, stress, and steroids.

A single injection of 2.5 mg perphenazine (PH)/kg body wt to rats on the day of estrus (day 0) did not result in increased serum progesterone 24 hr later. Continued daily injections, however, resulted in a 2.5-fold increase in serum progesterone between days 1 and 3 and a 1.6-fold increase between days 3 and 5 to a final concentration of 58 plus or minus 4 ng/ml on day 5 in serially anesthetized and bled rats. Neither daily administration of 5.0 nor 10.0 mg PH/kg body wt to rats subjected to the stressful conditions of this regimen resulted in further increases in serum progesterone, but the 5.0 mg dose of PH in unstressed rats bled only on day 5 resulted in a highly significant increase in serum progesterone to 110 plus or minus 7 ng/ml. In unstressed rats the increase in serum progesterone over control values after five daily injections of 2.5 mg PH/kg body wt could be attributed to decreased 20alpha-reduction of progesterone, but when the dose of PH was increased to 5.0 mg/kg, a highly significant increase in both progesterone and total progestins occurred indicating that prolactin can increase steroidogenesis as well as reduce 20alpha-hydroxysteroid dehydrogenase activity. After inhibition of ovulation, the 5.0 mg daily dose of PH resulted in serum progesterone of only 25 plus or minus 8 ng/ml on day 5 in unstressed rats. Thus, serum progesterone in ovulating rats treated with PH originated primarily in the corpora lutea. Perphenazine, 5.0 mg/kg, administered only on estrus and the first day of diestrus was sufficient to induce pseudopregnancy of 14.5 plus or minus 1.6 days. No evidence for gonadotropin stimulation of the ovaries of any rats was observed. The effect of stress on the progesterone response was not mimicked by administration of cortisol acetate and is assumed to be medicated by suppression of prolactin secretion.

Animals↗