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Biomedical subjects

B R Carr

Publications and source records attributed to B R Carr.

At least 145 records · Page 8Linked to original sources
PubMed1981

Plasma lipoprotein regulation of progesterone biosynthesis by human corpus luteum tissue in organ culture.

The role of plasma lipoproteins in supplying cholesterol for progesterone biosynthesis by human corpus luteum tissue in culture was investigated. Progesterone secretion by tissue fragments maintained in organ culture reached a maximum rate by the third day and subsequently declined. Maximal secretion of progesterone was dependent on the presence of both low density lipoprotein (LDL) and hCG in the culture medium, whereas high density lipoprotein (HDL) was ineffective in supporting progesterone biosynthesis. Human corpus luteum tissue degraded [125I]iodo-LDL by a mechanism which was saturable, and degradation of [125I]iodo-LDL was stimulated by hCG. Although 3-hydroxy-3-methylglutaryl coenzyme A reductase activity was present in microsomes prepared from fresh human corpus luteum tissue, the activity of this enzyme in microsomes prepared from tissue maintained in culture for 3 days was virtually undetectable. Fresh human corpus luteum tissue contained 3 times more unesterified cholesterol than esterified cholesterol. It is concluded that LDL, but not HDL, is the major source of cholesterol used by the human corpus luteum for progesterone biosynthesis.

Adult↗
PubMed1981

The role of cyclic adenosine 3',5'-monophosphate in cholesterol metabolism and steroidogenesis by the human fetal adrenal gland.

In the present investigation we studied the role of cAMP as a mediator of ACTH action in human fetal adrenal (HFA) tissue. We have characterized the response to ACTH, dibutyryl adenosine 3',5'-cyclic monophosphoric acid (dbcAMP), and cholera toxin (CT) with respect to steroidogenesis, low density lipoprotein (LDL) binding, degradation of LDL, and the rate of de novo synthesis of cholesterol. The rate of dehydroisoandrosterone sulfate secretion was similar in HFA tissue maintained in the presence of ACTH, dbcAMP, or CT. In contrast, cortisol secretion by HFA tissue was more sensitive to dbcAMP and CT than to ACTH. In membrane preparations obtained from HFA tissue maintained in the presence of ACTH, dbcAMP, or CT, there was a 2 to 3-fold increase of specific binding of [125I]iodo-LDL. In HFA tissue maintained in the presence of ACTH or CT, the rate of degradation of LDL was significantly increased compared to tissue maintained in the lipoprotein-poor serum alone. Finally, in HFA tissue maintained in the presence of ACTH, dbcAMP, or CT there was a 6- to 10-fold stimulation of the rate of incorporation of [14C]acetate into cholesterol. We conclude that steroidogenesis, LDL binding, and degradation, as well as de novo synthesis of cholesterol, are probably stimulated in HFA tissue via a cAMP-mediated pathway.

Adrenal Glands↗
PubMed1981

Synthesis of cholesterol in the human fetus: 3-hydroxy-3-methylglutaryl coenzyme A reductase activity of liver microsomes.

The specific activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase in microsome-enriched fractions prepared from normal human fetal liver tissue was assessed. The mean specific activity was 0.58 +/- 0.18 nmol mevalonate formed min-1 mg-1 protein. The activity of the enzyme was inhibited by preincubation of microsomes with ATP (4 mM) and was greatly reduced when microsomes were prepared from tissue homogenized in the presence of NaF (50 mM). It can be computed that the activity of HMG CoA reductase in human fetal liver microsomes is adequate to provide cholesterol to meet the requirements of the fetal adrenal for steroid precursor provided that cholesterol synthesized in the fetal liver appears in the plasma in the form of low density lipoprotein.

Cholesterol↗
PubMed1980

Inverse relation between low-density lipoprotein-cholesterol and dehydroisoandrosterone sulfate in human fetal plasma.

A striking inverse correlation was found in umbilical cord plasma between the concentrations of dehydroisoandrosterone sulfate and low-density lipoprotein (LDL)-cholesterol but not high-density lipoprotein-cholesterol or very low density lipoprotein-cholesterol. Dehydroisoandrosterone sulfate is a major secretory product of the human fetal adrenal and the principal precursor of placental estrogen production. The data suggest that the concentrations for LDL-cholesterol in fetal plasma are influenced by the rate of utilization of LDL-cholesterol by the fetal adrenal for steroidogenesis and are not necessarily related to a genetic predisposition for hypercholesterolemia or other lipoprotein disorders.

Adrenal Cortex↗
PubMed1980

Steroid secretion by ACTH-stimulated human fetal adrenal tissue during the first week in organ culture.

Fetal adrenal tissue has been reported to lose its in vivo secretory pattern by virtue of a loss of fetal zone cells after the first week in culture. Consequently, we studied the steroidogenic capacity and the responsiveness to ACTH of human fetal adrenal tissue during the first week in organ culture. The culture medium was removed daily and assayed for cortisol and dehydroisoandrosterone sulfate (DS). First, as the concentration of ACTH in the medium was increased from 0 to 1 micrograms/ml steroid secretion increased. When tissue fragments were maintained in the absence of ACTH for 3 to 4 days, there was a striking increase in steroid secretion upon addition of ACTH to the medium, with larger rates of secretion of cortisol than DS being observed. Second, the steroidogenic capacity of the separate zones of the fetal adrenal gland was assessed. Tissue from the fetal zone secreted large amounts of DS and small amounts of cortisol, whereas neocortex tissue secreted similar quantities of DS and cortisol. Third, fetal zone tissue was maintained the absence of ACTH for 4 days and thereafter ACTH was added to the media for an additional 6 days. In this experiment, there was a marked increase in DS secretion rate after the addition of ACTH and a smaller increase in cortisol secretion.

Adrenal Glands↗
PubMed1980

Metabolism of high density lipoprotein by human fetal adrenal tissue.

The role of lipoproteins as a source of the cholesterol utilized for steroidogenesis by human fetal adrenal (HFA) tissue was investigated previously. It was found that low density lipoprotein (LDL) was the lipoprotein preferred as a source of cholesterol for steroidogenesis by the HFA. [125I]Iodo-LDL was taken up and degraded by HFA tissue in organ culture, and the degradation of [125I]iodo-LDL was stimulated when ACTH (1 microgram X ml-1) was present in the culture medium. Others have shown that high density lipoprotein (HDL) is utilized as a source of cholesterol for steroidogenesis by rat adrenocortical cells in vitro and by the adrenals of the adult rat in vivo. In the present investigation we evaluated the metabolism of [125I]iodo-HDL by HFA tissue. [125I]iodo-HDL uptake by the HFA tissue increased in a linear manner with time and as the concentration of [125I]iodo-HDL in the culture medium was increased. However, there was little degradation of [125I]iodo-HDL by HFA. Moreover, preincubation of HFA tissue in medium containing ACTH (1 microgram X ml-1) or HDL, in various concentrations, did not affect the rate of uptake and degradation of [125I]iodo-HDL. The rate of degradation of [125I]iodo-LDL was found to decrease to low levels as the concentration of nonradiolabeled LDL in the culture medium was increased, whereas nonradiolabeled HDL had little effect on the degradation of [125I]iodo-LDL. HFA tissue fragments were incubated in medium containing ACTH plus lipoprotein-poor serum (LPPS) alone or LPPS plus HDL in various concentrations (50-1000 microgram X ml-1). The medium was changed daily and assayed for dehydroisoandrosterone sulfate and cortisol. In the presence of HDL, steroid secretion rates were no greater than those attained by HFA maintained in medium containing LPPS. It is concluded that the HFA utilizes cholesterol derived from LDL for steroidogenesis and that HDL is not metabolized efficiently by the human fetal adrenal.

Adrenal Glands↗
PubMed1980

Regulation of steroid secretion by adrenal tissue of a human anencephalic fetus.

ACTH-stimulated adrenal tissue of a human anencephalic fetus, when maintained in organ culture, secreted appreciable quantities of cortisol but little dehydroisoandrosterone sulfate or pregnenolone sulfate. In the absence of ACTH, cortisol secretion was severely attenuated. Arginine vasopressin or alpha MSH, when added to the culture medium, did not stimulate steroid secretion. When whole human serum was present in the culture medium bathing the adrenal tissue of the anencephalic fetus, the rate of cortisol secretion was similar to that attained when lipoprotein-poor serum was in the medium. Based on these findings, it is concluded that in the presence of ACTH, the adrenals of the anencephalic fetus secrete principally cortisol, and the failure of dehydroisoandrosterone sulfate and pregnenolone sulfate secretion is due to the absence of the fetal zone. The lack of stimulation of cortisol secretion by lipoprotein is probably due to a reduced number of low density lipoprotein receptors resulting from diminished ACTH stimulation before birth.

Adrenal Glands↗
PubMed1980

Plasma lipoproteins in follicular fluid of human ovaries.

Human corpus luteum tissue, maintained in organ culture, is dependent upon low-density lipoprotein (LDL) as a source of cholesterol for maximal progesterone secretion whereas high-density lipoprotein (HDL) does not support progesterone biosynthesis by human corpus luteum tissue. In the present investigation, follicular fluid of human ovaries was found to contain little or no LDL or very low-density lipoprotein. The concentration of HDL in follicular fluid approached that found in plasma. We suggest that one reason that granulosa cells of the preovulatory follicle produce limited quantities of progesterone is because of the absence of LDL-cholesterol in follicular fluid. Following ovulation, vascularization of the corpus luteum provides a means by which LDL is available to the luteinized granulosa cells and thence progesterone biosynthesis can commence.

Body Fluids↗
PubMed1980

Steroid production in a woman with gonadal dysgenesis, breast development, and clitoral hypertrophy.

Androgen and estrogen production was measured in a 46,XX woman with gonadal dysgenesis, breast development, and clitoral hypertrophy. The production rates of androstenedione (438 micrograms/24 hr), estrone (26 micrograms/24 hr), and estradiol-17 beta (13 micrograms/24 hr) were low compared to values obtained in normal young women. The production rate of testosterone (239 micrograms/24 hr) was similar to that of normal women. Bilateral nodular streaks were found in the usual anatomic site occupied by ovaries. By microscopic examination of the streaks, fibrous tissue containing nests of hilar cells was found. The karyotype of skin, peripheral leukocytes, and gonadal streak fibroblasts in culture was 46,XX. The possible causes and implications of breast development and clitoral enlargement in subjects with gonadal dysgenesis are discussed.

Adult↗
PubMed1979

The role of serum lipoproteins in steroidogenesis by the human fetal adrenal cortex.

In the present investigation it was found that human fetal adrenal tissue maintained in organ culture secreted appreciable quantities of dehydroisoandrosterone sulfate (DS) and cortisol. Pregnenolone was also secreted in significant amounts, principally as the sulfate ester. The highest rate of secretion of these steroids by fetal adrenal tissue occurred when both ACTH and whole human serum were present in the culture medium. In the absence of ACTH, steroid secretion was low. When whole serum was replaced by lipoprotein-poor serum, the steroidogenic response to ACTH was markedly attenuated but not abolished. On the basis of these findings, it is concluded (1) that the human fetal adrenal can synthesize steroid hormones de novo from cholesterol, (2) that ACTH is an important stimulant of steroidogenesis by the human fetal adrenal, and (3) that plasma lipoproteins are a major source of the cholesterol utilized by the human fetal adrenal for steroidogenesis. Hence, it is likely that factors which regulate the production of fetal plasma lipoproteins are important determinants of fetal adrenal steroidogenic activity.

Adrenal Cortex Hormones↗
PubMed1979

Plasma levels of adrenocorticotropin and cortisol in women receiving oral contraceptive steroid treatment.

The secretion rate and plasma concentration of the adrenocortical steroid cortisol is modified in subjects treated with estrogenic and/or progestational steroids. The effects of contraceptive steroids on the secretion of ACTH are poorly documented, however, In the current investigation, we found that concentrations of ACTH and cortisol in plasma obtained at 0800--0900 h from a group of women with normal cyclic menses (n = 4) ranged from 78--120 pg/ml and 77--137 ng/ml, respectively. Although significant cyclic changes in the plasma levels of LH, FSH, 17 beta-estradiol, and progesterone occurred during the ovarian cycle, no obvious cyclic fluctuations in plasma levels of ACTH or cortisol were observed. In women treated with Norinyl 1 + 80 (1.0 mg norethindrone plus 0.08 mg mestranol), plasma concentrations of LH, FSH, 17 beta-estradiol, and progesterone were significantly lower (P less than 0.001) than plasma levels of these hormones in normal women during the ovarian cycle. The mean daily plasma concentrations of ACTH were significantly lower (P less than 0.001), whereas plasma cortisol levels were significantly higher (P less than 0.001) in women treated with oral contraceptive steroids compared to the levels of these hormones in the untreated ovulatory women.

Adrenocorticotropic Hormone↗
PubMed1978

The effect of oral contraceptive treatment on the serum concentration of dehydroisoandrosterone sulfate.

Dehydroisoandrosterone sulfate (DS), the major C19-steroid in the human circulation, was measured in serum obtained from blood samples collected daily (8 to 10 A.M.) throughout the menstrual cycles of eight normal, presumably ovulatory women and daily throughout the treatment cycles in four women taking an oral contraceptive (norethindrone, 1 mg., plus mestranol, 80 mcg.). The serum concentrations of DS in the ovulatory women ranged from 1,025 to 4,200 ng. per milliliter; mean, 2,062 +/- 137 ng. per milliliter (mean and standard error; n = 213). Serum DS concentrations during the follicular and luteal phases of the menstrual cycles of these women were similar. In women taking the oral contraceptive, the plasma DS concentrations ranged from 475 to 1,400 ng. per milliliter (mean, 895 +/- 83; n = 119). The 24 hour secretory pattern of DS was evaluated in one subject during a nontreatment cycle and again after 20 days of oral contraceptive treatment. In this subject, the mean serum DS level was 34 per cent lower during oral contraceptive treatment than the level before treatment. The decrease in the serum concentration of DS during oral contraceptive treatment likely results from a reduction in adrenal DS secretion since DS secretion by the normal human ovary is negligible and ovarian dehydroisoandrosterone secretion is small. Therefore, it is likely that the reduced serum DS levels in women taking oral contraceptives are the consequence of reduced adrenal secretion of DS resulting from reduced release of adrenocorticotropic hormone.

Adrenal Cortex↗