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Biomedical subjects

B R Carr

Publications and source records attributed to B R Carr.

At least 73 records · Page 4Linked to original sources
PubMed1991

Protein kinase C in uterine and systemic arteries during ovarian cycle and pregnancy.

Elevated uterine blood flow is associated with increases in local estrogen-to-progesterone ratios during the follicular phase of the ovarian cycle and late pregnancy. Because protein kinase C (PKC) activation increases arterial tone, decreased PKC activity may mediate vasodilation. Therefore, we determined uterine (UA) and systemic artery (SA, omental) PKC activity (pmol.mg protein-1.min-1) during the follicular (n = 6), early luteal (n = 4), and late luteal (n = 3) phases of the sheep ovarian cycle, and at 110 +/- 3 (n = 4) and 130 +/- 1 (n = 8) (+/- SE) days of ovine gestation. The stage of the ovarian cycle was verified by the presence of follicles (high estrogen) or corpora lutea (high progesterone) on the ovary and by plasma estrogen and progesterone concentrations. UA-PKC activity (pmol.mg protein-1.min-1) during the follicular phase was 100 +/- 18 and increased progressively to 155 +/- 28 during the early luteal phase and to 219 +/- 37 (P less than 0.05) during the late luteal phase; SA-PKC activity was unchanged. A local utero-ovarian relationship was observed, i.e., UA-PKC activity was lower (P less than 0.001) in UA ipsilateral to ovaries with only follicles (105 +/- 14) when compared with UA adjacent to ovaries with corpora lutea (224 +/- 26), which was similar to SA-PKC activity (184 +/- 35). UA-PKC activity fell from 344 +/- 70 at 110 days to 109 +/- 12 at 130 days gestation (P less than 0.05); SA-PKC activity was unchanged. During the ovarian cycle and latter one-third of ovine pregnancy, increased estrogen production is associated with decreased UA-PKC activity; thus local ovarian and placental steroids may alter PKC activity, thereby regulating UA tone and blood flow.

Animals↗
PubMed1991

Glucocorticoids inhibit lipopolysaccharide-induced production of tumor necrosis factor-alpha by human fetal Kupffer cells.

Inflammatory mediators, such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) are secreted by fixed tissue macrophages and exhibit local autocrine and paracrine effects as well as distant endocrine effects. Human fetal Kupffer cells, the fixed tissue macrophages of the liver, may play a role as modulators of immune and endocrine function in early embryonic and fetal development. In the present study we isolated human fetal Kupffer cells to greater than 90% purity and prepared short term cultures to investigate the effect of glucocorticoids on the secretion of the cytokine TNF alpha. Fetal Kupffer cells secreted TNF alpha and IL-1 beta after culture with bacterial lipopolysaccharide (LPS), indicating that these cells express mature macrophage function. Cortisol and dexamethasone dramatically suppressed the LPS-stimulated secretion of TNF alpha by fetal Kupffer cells. The inhibitory effects of glucocorticoids appeared to be specific, since estrogen, progesterone, and testosterone had no effect on LPS stimulation of TNF alpha production. None of the steroids tested altered basal production or enhanced the LPS-stimulated production of TNF alpha by fetal Kupffer cells. The inhibition by glucocorticoids could be reversed by the addition of RU 486, indicating that this effect was mediated by the glucocorticoid receptor. These results demonstrate that human fetal macrophages demonstrate mature macrophage function in early gestation; they can be activated to produce TNF alpha by a well characterized modulator of cellular function (LPS) and suppressed by glucocorticoids.

Dexamethasone↗
PubMed1991

Effect of superovulation with human menopausal gonadotropins on growth hormone levels in women.

GH synthesis and secretion are influenced by several factors, including age, body weight, and sex steroid hormones. Endogenous and exogenous estrogens influence the circulating levels of GH. The purpose of the present investigation was to define the relationship between serum GH and estradiol levels during the follicular phase in women with normal ovulatory menstrual cycles compared with that in women undergoing superovulation with human menopausal gonadotropins (hMG) alone or hMG plus GnRH agonists during treatment for infertility. Serum GH and estradiol levels were determined by immunoassay in eight women during the follicular phase of a spontaneous natural cycle (group I). Thirty women underwent ovulation induction with hMG alone (group II), and 30 women received GnRH agonists followed by hMG (group III). During the follicular phase estradiol levels increased gradually in group I and reached a peak estradiol level of 1.19 +/- 0.2 nmol/L (mean +/- SEM). As expected, estradiol levels rose faster and reached higher levels in groups II and III (5.44 +/- 0.62 and 8.73 +/- 0.91 nmol/L, respectively). Whereas serum GH levels increased minimally in group I, reaching a peak level of 2.54 +/- 1.15 nmol/L, serum GH concentrations increased markedly after day 8 in groups II and III, reaching peak levels of 8.70 +/- 1.58 and 7.54 +/- 1.12 nmol/L, respectively (P less than 0.01). Basal to peak GH levels were higher in groups II and III than in group I. In summary, there are modest increases in GH levels during the follicular phase of the normal menstrual cycle, but the levels are markedly increased during superovulation with hMG or hMG plus GnRH agonists, and parallel increases in estradiol levels.

Adult↗
PubMed1991

3 beta-Hydroxysteroid dehydrogenase activity in glandular and extraglandular human fetal tissues.

The expression of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) in steroidogenic tissues is an absolute requirement for mammalian reproduction, fetal growth, and life maintenance. We sought to identify extraglandular tissue sites in the human fetus where 3 beta HSD is expressed. To this effect, we conducted in vitro studies by use of homogenates prepared from second trimester fetal tissues. To facilitate the determination of 3 beta HSD activity, an abbreviated technique was developed that consisted in the use of [3 alpha-3H]dehydroepiandrosterone [( 3 alpha-3H]DHEA) as the substrate and NAD+ as the cofactor. With these reagents, the enzymatic reaction leads to the production of both nonradiolabeled androstenedione and NAD3H in equimolar amounts, and the radioactivity associated with NAD3H is used for quantification of 3 beta HSD activity. The kinetic isotope effect introduced by substitution of tritium for hydrogen at the C-3 alpha position of DHEA, determined with six different tissues, was 2.5 +/- 0.7 (mean +/- SD). The specific activities of the enzyme in peripheral tissues and ovary were relatively low, in the range of 0.03 nmol/mg protein.h for stomach (n = 2) to 0.18 +/- 0.14 nmol/mg protein.h for liver (mean +/- SD; n = 13), while in fetal testis and placenta the specific activities were relatively high, viz. 3.4 +/- 0.7 nmol/mg protein.h (mean +/- SD; n = 4) and 2.8 +/- 1.8 nmol/mg protein.h (mean +/- SD; n = 13), respectively. The findings of this study serve to demonstrate that 3 beta HSD is distributed widely among tissues of the human fetus. Although the enzymatic activity was easily demonstrated in peripheral tissues by the use of radiolabeled DHEA as the substrate, 3 beta HSD protein was not readily detected by Western analysis.

3-Hydroxysteroid Dehydrogenases↗
PubMed1990

The effect of gonadotropin-releasing hormone agonists on growth hormone secretion in adult premenopausal women.

Suppression of the pituitary-gonadal axis by the administration of gonadotropin-releasing hormone agonists (GnRH-a) has been used for a variety of endocrinological and gynecological disorders. The suppressive effect of GnRH-a on luteinizing hormone, follicle-stimulating hormone, and sex steroid production is well documented. However, little is known regarding the effect of GnRH-a on other aspects of pituitary function. The purpose of the present study was to determine the effect of GnRH-a treatment on growth hormone-releasing hormone (GH-RH)-stimulated GH release in premenopausal women. Eight control women and seven women, who were receiving a GnRH-a, were recruited. Before and after a bolus infusion of human GH-RH, blood samples were obtained over 3 hours and analyzed for GH by immunoassay. Basal GH and insulin-like growth factor levels were not statistically different between the two groups. However, basal levels of estradiol and the integrated GH response after GH-RH were significantly lower in the GnRH-a treated women. The reduction in GH-RH-stimulated GH release in GnRH-a treated women may be attributed to diminished endogenous estrogen secretion, or to direct pituitary suppression by GnRH-a, or both.

Adult↗
PubMed1990

3 beta-hydroxysteroid dehydrogenase/isomerase in the fetal zone and neocortex of the human fetal adrenal gland.

The fetal zone of the human fetal adrenal (HFA) gland is established to have decreased 3 beta-hydroxysteroid dehydrogenase/delta 4-5 isomerase (3 beta HSD) activity compared to the neocortex or definitive zone. 3 beta HSD activity, however, can be induced in primary cell culture through treatment with ACTH. Therefore, the HFA with two distinct steroidogenic zones with differences in 3 beta HSD activity as well as the capacity to increase 3 beta HSD activity in response to ACTH provides an excellent model to study the regulation of this enzyme. The presence of 3 beta HSD in the fetal and neocortex zones of the HFA was examined using a polyclonal antibody raised against purified human placental microsomal 3 beta HSD. After homogenates of the fetal and neocortical zones of the HFA were electrophoresed on a sodium dodecyl sulfate-polyacrylamide gel and immunoblotted, the presence of the 3 beta HSD protein with a molecular size of 45 kDa could be demonstrated only in the neocortical zone. ACTH treatment (greater than 2 days) of fetal and neocortical zone explant cultures produced increases in cortisol secretion associated with the respective levels of immunodetectable 3 beta HSD protein. Cortisol and dehydroepiandrosterone sulfate were the respective principal steroid products of neocortical and fetal zone explants. After ACTH treatment, immunodetectable 3 beta HSD was induced to a greater magnitude in the neocortex. These findings provide evidence that the lack of 3 beta HSD activity in the fetal zone, previously considered to be the result of the presence of an endogenous inhibitor, is due to an absence of the protein in this portion of the gland. The lack or minimal expression of 3 beta HSD in the fetal zone of HFA may be due to the action (or lack thereof) of a tissue-specific factor regulating the synthesis of 3 beta HSD.

3-Hydroxysteroid Dehydrogenases↗
PubMed1990

Transforming growth factor-beta inhibits steroid 17 alpha-hydroxylase cytochrome P-450 expression in ovine adrenocortical cells.

The maintenance of optimal steroidogenesis in adrenocortical cells primarily depends on the chronic action of ACTH to promote the synthesis of the various steroid-metabolizing cytochrome P-450 enzymes. In the steroidogenic pathway, 17 alpha-hydroxylase cytochrome P-450 (P-450(17) alpha) is a key enzyme controlling the formation of cortisol and androgens. Recently, we demonstrated that transforming growth factor-beta (TGF beta) is a potent inhibitor of steroid production in ovine adrenocortical cells. In the present study we used a polyclonal antibody to P450(17) alpha to determine adrenal cell P-450(17) alpha enzyme content by Western analysis. In addition, we used a cDNA probe encoding for bovine P-450(17) alpha mRNA to determine levels of P-450(17) alpha mRNA in sheep ovarian adrenocortical cells in primary culture. When cells were cultured in a serum-free medium in the presence of ACTH for 48 h, P-450(17) alpha activity, enzyme content, and mRNA levels for P-450(17) alpha increased by 3- to more than 10-fold. TGF beta decreased the basal level and completely blocked the stimulatory action of ACTH on P-450(17) alpha enzyme activity. The effects of TGF beta on P-450(17) alpha enzyme content and mRNA levels were manifested in a dose-dependent manner, with maximal inhibition observed using 1 ng/ml TGF beta. Importantly, the inhibitory effects of TGF beta on P-450(17) alpha were not overcome by (Bu)2cAMP. These findings indicate that TGF beta is a potent negative regulator of P-450, and the inhibitory action appears to be at the level of P-450(17) alpha gene expression. The ability of TGF beta to suppress the positive stimulatory action of ACTH suggests that TGF beta could play a role in determining the pathway of steroidogenesis and, thereby, the specific steroids secreted by adrenocortical cells.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Secretory immune system of the female reproductive tract. II. Local immune system in normal and infected fallopian tube.

The existence of a secretory immune system in the female genital tract has been demonstrated by the predominance of immunoglobulin (Ig)A-producing plasma cells in human fallopian tube, uterine cervix, and vagina. Epithelium lining fallopian tubes expresses a receptor for IgA, secretory component (SC), and thus resembles other secretory tissues such as intestine, mammary, lacrimal, and salivary glands. The present study extends the characterization of the local immune system in the fallopian tube and assesses its response to infection. We examined normal and infected fallopian tubes from surgical specimens, obtained at tubal ligation and abdominal hysterectomy, for the presence of Ig-producing cells, T cells, and natural killer cells. All tubular segments contained a predominance of IgA plasma cells in the subepithelial lamina propria. The epithelial cells were strongly positive for SC. Luminal contents stained positively for IgA, SC, and J chain, suggesting that this material contained secretory IgA. Submucosal plasma cells of IgM and IgG classes were less frequent than IgA. T cells were present in numbers approximately twofold greater than plasma cells in normal fallopian tubes. T-suppressor (CD8+) cells, which may function in the induction of immune tolerance, were present in the intraepithelial spaces. Infected segments of fallopian tubes demonstrated six- to tenfold increased numbers of plasma cells of all classes. These data suggest that a local immune system is functioning in the human fallopian tube and may provide a first line of defense against tubal infection and the prevention of tubal factor infertility.

Epithelium↗
PubMed1990

Amenorrhea.

Amenorrhea, the lack of menstruation, is a gynecologic disorder that may arise from a variety of causes. If a logical and orderly schema is followed, the correct diagnosis and appropriate management plan can be formulated.

Amenorrhea↗
PubMed1989

Aromatase in human fetal tissues.

The placenta has been shown to be the major source of estrogen production during pregnancy. This investigation was undertaken to compare the content and activity of aromatase in the placenta and various other human fetal tissues. Tissues were obtained from first- and second-trimester human abortuses. The amount of aromatase P-450 (aromatase cytochrome P-450) in tissue homogenates was determined after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting by use of a polyclonal antibody directed against aromatase cytochrome P-450. The activity of aromatase in microsomal preparations was assayed by determining the rate of incorporation of tritium from 1-[3H]androstenedione into [3H]water. The greatest amount of aromatase cytochrome P-450 (55 kd) was detected in placenta and lesser amounts were detected in other tissues. Aromatase activity also was highest in placental microsome fractions (368 +/- 62.4 pmol/mg/hr [mean +/- SE], n = 9). A significant amount of aromatase activity was also detected in fetal liver (19 +/- 4.8 pmol/mg/hr, n = 7). Much less activity was found in brain (2.8 +/- 1.0 pmol/mg/hr, n = 6) and intestine (2.7 +/- 1.3 pmol/mg/hr, n = 7). Minimal activity was noted in adrenal (n = 5), spleen (n = 4), stomach (n = 4), and muscle (n = 5) (1.2 to 1.5 pmol/mg/hr). Activity in kidney (n = 7), heart (n = 4), and lung (n = 4) was extremely low (less than 0.8 pmol/mg/hr). In conclusion, the placenta is a major site of conversion of C19 steroid precursors to estrogens because of the amount of enzyme and the high rate of activity of aromatase compared with those of other fetal tissues. However, considering the size and rate of aromatase activity in other fetal tissues such as liver, brain, and intestine, these tissues also may contribute to the total estrogen production in the fetal-placental unit.

Aromatase↗
PubMed1989

Effect of oral contraceptives on adrenocorticotropin and growth hormone secretion following CRH and GHRH administration.

Previous investigations have demonstrated that basal ACTH plasma levels are reduced and that GH levels are either increased or unchanged in women taking oral contraceptives. The purpose of the present investigation was to determine the secretion of ACTH and GH following an intravenous infusion of human corticotropin releasing hormone (CRH) and human growth hormone releasing hormone (GHRH) in control women (N = 8) and in women taking a triphasic oral contraceptive (N = 9). The studies were initiated between 7:00 and 9:00 a.m. and all women were fasting. An intravenous catheter attached to a 3-way stopcock was used for blood sampling and to inject a bolus of CRH and GHRH (1 microgram/kg). Plasma samples were frozen immediately and stored at -70 degrees C until assayed for content of ACTH and GH by radioimmunoassay. The plasma levels of ACTH and GH increased following infusion of CRH and GHRH in all women. The mean plasma levels of growth hormone were not statistically different in oral contraceptive users compared to normal women. In contrast, ACTH plasma levels in oral contraceptive users were reduced approximately 25% overall, and significantly lower (p less than 0.04) at 120 minutes following the CRH infusion compared to controls. In conclusion, the GHRH-stimulated GH release was similar in normal women and oral contraceptive users. CRH-stimulated ACTH release was modestly reduced in oral contraceptive users compared to normal women suggesting that estrogens and progestogens may have a suppressive effect on the release of ACTH by the pituitary.

Adrenocorticotropic Hormone↗
PubMed1989

Testosterone synthesis and adenylate cyclase activity in the early human fetal testis appear to be independent of human chorionic gonadotropin control.

Androgen secretion by the fetal testis is essential for male phenotypic differentiation. In the human fetus testosterone formation is initiated soon after the differentiation of the testis (approximately 8 weeks of gestation), and the maximal testosterone content in fetal testes is achieved between 10 and 15 weeks of fetal life. The testosterone content of the fetal testis declines at the beginning of the third trimester and remains low until after birth. In an effort to understand the regulation of the onset of testosterone formation in the human fetal testis we measured adenylate cyclase activity in response to hCG stimulation in homogenates of fetal testes obtained from first and second trimester human abortuses. Basal adenylate cyclase activity was 50 pmol/mg protein.min at 10 weeks gestation, the peak activity was 137 pmol/mg protein.min at 12 weeks gestation, and activity declined thereafter to 8 pmol/mg protein.min by 16 weeks gestation. NaF-stimulated (0.6 mmol/L) and forskolin-stimulated (50 mumol/L) activities were 4- to 8-fold greater than basal adenylate cyclase activities. The maximal forskolin-stimulated activity occurred at 11 weeks (803 pmol/mg protein.min), and it fell to 35 pmol/mg protein.min by 17 weeks gestation. In contrast, hCG-stimulated (1 mumol/L) adenylate cyclase activity was only slightly greater than basal rates at all ages examined. In addition, hCG did not stimulate baseline testosterone formation in minces of testes obtained between 12 and 18 weeks of gestation. These findings suggest that the onset of testosterone formation in human fetal testes may be independent of gonadotropin control.

Adenylyl Cyclases↗
PubMed1989

Activity of 17 beta-hydroxysteroid oxidoreductase in tissues of the human fetus.

The interconversion of oestrone and oestradiol, androstenedione and testosterone, and dehydroepiandrosterone and 5-androstene-3 beta,17 beta-diol in mammalian tissues is catalysed by 17 beta-hydroxysteroid oxidoreductase (17 beta-HSOR). To identify tissue sites of 17 beta-HSOR activity in the human fetus, microsomal fractions from 15 different fetal tissues obtained from first and second trimester pregnancies were used for evaluation of enzymatic activity by use of [17 alpha-3H] oestradiol as the substrate and NADP+ as the co-factor. With these reagents, the enzyme-catalysed reaction led to the production of both non-radiolabelled oestrone and NADP3H in equimolar amounts; the radioactivity associated with NADP3H was used to quantify 17 beta-HSOR activity. Activity of 17 beta-HSOR was present in microsomes of all the tissues evaluated. The specific activity of the enzyme was highest in liver and placental microsomes. The interconversion of oestradiol and oestrone in microsomal fractions of nine different fetal tissues was studied by the use of substrates labelled with tritium at stable nuclear positions ([6,7-3H]oestradiol and [6,7-3H]oestrone). The products, [3H]oestrone and [3H]oestradiol, were quantified by the use of established techniques; other metabolites formed in these incubations were not identified. The reductive pathway of metabolism (oestrone to oestradiol) appeared to be favoured in microsomal fractions prepared from placenta, fetal zone of the adrenal gland and, possibly, lung. The oxidative pathway (oestradiol to oestrone) appeared to be favoured in microsomes prepared from liver, intestine, stomach, kidney, brain and heart. 17 beta-HSOR activity in fetal liver also was assessed by the use of fresh and frozen-thawed tissue, homogenate, subcellular fractions, and, also, in primary hepatocytes maintained in culture; the specific activity of the enzyme was highest in the microsomal fraction of liver tissue and 17 beta-HSOR activity in liver microsomes was linear with time of incubation up to 1 h. In hepatocytes, the enzymatic activity was linear with time of incubation up to 2 h and with cell number up to 2.5 x 10(5) cells/ml; the apparent Michaelis constant of hepatocyte 17 beta-HSOR for oestradiol was 11 mumol/l. The specific activity of 17 beta-HSOR did not change after pretreatment of hepatocytes for 24 h with insulin, glucagon or dexamethasone.

17-Hydroxysteroid Dehydrogenases↗
PubMed1989

Familial posterior labial fusion.

Partial virilization at birth of a genotypic female resulting in varying degrees of posterior labial fusion and clitoral enlargement is most commonly due to excess androgen production from congenital adrenal hyperplasia. Rarely, labial fusion arises secondary to maternal androgen ingestion or an androgen-secreting tumor during pregnancy. We report a case of posterior labial fusion without clitorimegaly in a 12-year-old girl in which there was no evidence of androgen excess. The family history was remarkable for a similar congenital defect in two aunts and their daughters, suggesting an autosomal dominant trait with incomplete penetrance.

Child↗
PubMed1988

The effects of alpha-human atrial natriuretic polypeptide on steroidogenesis by fetal zone cells of the human fetal adrenal gland.

The human fetal adrenal gland is primarily composed of fetal zone cells, which exhibit a high rate of steroidogenesis and a rapid growth rate during fetal life. alpha-Human atrial natriuretic polypeptide has been shown to inhibit basal and adrenocorticotropic hormone-stimulated steroidogenesis in the human adult and in some human adrenal adenoma cells. The purpose of this investigation was to determine the effect of atrial natriuretic polypeptide on steroidogenesis by fetal zone cells. Dispersed fetal zone cells were incubated in Krebs-Ringer's medium with adrenocorticotropic hormone, forskolin, 22R-hydroxycholesterol, or dibutyryl cyclic adenosine monophosphate and in the presence of atrial natriuretic polypeptide. The medium was analyzed for content of dehydroepiandrosterone sulfate and cortisol by radioimmunoassay. The addition of adrenocorticotropic hormone, forskolin, 22R-hydroxycholesterol, or dibutyryl cyclic adenosine monophosphate increased the secretion of dehydroepiandrosterone sulfate and cortisol twofold to threefold and twofold to sixfold, respectively, above basal rates. Atrial natriuretic polypeptide significantly inhibited basal dehydroepiandrosterone sulfate and cortisol secretion. When cells were incubated in the presence of adrenocorticotropic hormone, forskolin, 22R-hydroxycholesterol, or dibutyryl cyclic adenosine monophosphate plus atrial natriuretic polypeptide, cortisol secretion was inhibited 50% to 90% and dehydroepiandrosterone sulfate was inhibited 25% to 50%. Atrial natriuretic polypeptide had no effect on the metabolism of progesterone tagged with carbon 14 in fetal zone cells. In conclusion, atrial natriuretic polypeptide inhibited basal and adrenocorticotropic hormone-stimulated steroid secretion by fetal zone cells. Furthermore, these results suggested that the action of atrial natriuretic polypeptide was by inhibition of cholesterol side-chain cleavage or transfer of cholesterol to the mitochondrion.

Adrenal Glands↗
PubMed1988

Apolipoprotein A-1 in umbilical cord blood of newborn infants: relation to gestational age and high-density lipoprotein cholesterol.

Apolipoprotein A-1 (Apo A-1) is the major protein constituent of high-density lipoprotein (HDL) and Apo A-1 plays an important role in lipid metabolism and may be protective against atherosclerosis in adults. However, little is known about HDL and Apo A-1 in the developing human fetus. Herein we investigated the relationship of Apo A-1 levels in umbilical cord blood at delivery to gestational age and HDL cholesterol. Fetal plasma levels of Apo A-1, which were not correlated with those in maternal plasma, were significantly lower among newborns delivered at 21-26 wk gestation (52 +/- 4.4 mg/dl, mean +/- SE) than in those delivered at 33-34 wk gestation (87 +/- 5.8 mg/dl). Thereafter, the mean umbilical cord plasma levels of Apo A-1 remained relatively constant (101 mg/dl at 39-40 wk of gestation). We found no significant correlations between Apo A-1 levels and fetal sex, race, or delivery method. At equivalent gestational ages and birth weights, however, Apo A-1 levels in white newborns tended to be lower than those in black infants. The Apo A-1/HDL cholesterol ratio in umbilical cord blood rose progressively from 2.5 (27-28 wk gestation) to 3.8 at term, due largely to increased Apo A-1 levels but little change in the mean HDL cholesterol levels, which ranged from 22-24 mg/dl at each gestational period. These results are suggestive that fetal plasma Apo A-1 is derived solely from fetal sources and that the rate of production and/or clearance of Apo A-1 is altered during the latter third of human intrauterine development.

Apolipoprotein A-I↗
PubMed1988

Protein kinase-C in the human fetal adrenal gland.

The fetal zone (FZ) of the human fetal adrenal gland undergoes rapid growth and exhibits a high rate of steroidogenesis throughout fetal life. In addition to cAMP-dependent processes regulating steroidogenesis and possibly growth of the FZ, evidence is accumulating that cAMP-independent mechanisms are also involved. The purpose of this study was to determine if the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent stimulator of protein kinase-C activity, stimulates steroidogenesis in FZ cells and to characterize protein kinase-C activity in FZ, neocortex zone, and anencephalic adrenal tissues. Adrenal glands were obtained from first and second trimester abortions and two anencephalic fetuses. The FZ was dissected from the neocortex. In some experiments, dispersed FZ cells were incubated in the presence and absence of ACTH and TPA for 3 h. TPA and ACTH stimulated steroidogenesis 2- and 5-fold, respectively. In other experiments, the separated zones and anencephalic adrenal tissues were homogenized, and the homogenates were subjected to DEAE-cellulose column chromatography. A single peak with phospholipid- and calcium-dependent activity was found. Subcellular distribution studies demonstrated greatest activity in the cytosolic fraction. The specific activity of protein kinase-C was significantly greater in FZ than neocortex zone, whether expressed per mg protein or per microgram DNA content. The activity in anencephalic tissue was low. In addition, protein kinase-C (80,000-dalton molecular size protein) was detected in adrenal tissues after electrophoresis and immunoblotting using an antibody directed against protein kinase-C. Greater amounts of protein kinase-C were detected in FZ tissue than in NC or anencephalic adrenal tissue. These results indicate that the lower activities of protein kinase-C in neocortex and anencephalic adrenal tissues were due to low amounts of enzyme rather than inactive enzyme. In summary, TPA-stimulated steroidogenesis in fetal zone cells and fetal zone cells contained greater activity and a greater amount of protein kinase-C than neocortex cells. Minimal activity and enzyme protein were found in anencephalic tissues. These results suggest that cAMP-independent mechanisms may play a role in fetal adrenal steroidogenesis.

Adrenal Cortex↗