Latter Part Of Gestation Research Articles

Adrenal steroidogenesis in very low birth weight preterm infants.

Adrenal steroidogenesis was evaluated in 25 sick premature infants with a gestational age of less than 30 weeks. ACTH stimulation tests were performed on the fourth day of life using synthetic ACTH (36 micrograms/kg). Considering the stress and degree of illness, preterm newborns had low basal cortisol levels (mean +/- SEM, 207.4 +/- 23.5 nmol/L), and their levels were similar to basal levels reported for healthy full-term newborns (170.7 +/- 26.8 nmol/L; P = 0.31; reference data from Endocrine Sciences, Inc., Calabasas Hills, CA). However, compared to term neonates, preterm infants had markedly elevated basal levels of 17-hydroxypregnenolone (54.3 +/- 11.2 nmol/L), 17-hydroxyprogesterone (19.7 +/- 4.0 nmol/L), and 11-deoxycortisol (19.1 +/- 3.3 nmol/L), which were 7-, 18-, and 8-fold higher, respectively, than values for term infants. The activity of 3 beta-hydroxysteroid dehydrogenase was not significantly reduced in extremely premature neonates (mean basal ratio of 17-hydroxypregnenolone/17-hydroxyprogesterone, 2.9 +/- 0.2; ACTH-stimulated ratio, 6.5 +/- 0.4). In contrast, the mean basal substrate/product ratio of 11-deoxycortisol was markedly elevated in the preterm infants (11.9 +/- 2.2, ratio x 10(-2) compared to that in the full-term infants (2.1 +/- 0.4, ratio x 10(-2); P < 0.001). These findings are consistent with decreased activity of 11 beta-hydroxylase (11 beta OH) in preterm infants born at less than 30 weeks gestation. Decreased 11 beta OH activity appears to be more prominent than the deficiency of 3 beta-hydroxysteroid dehydrogenase that has been found in infants with lesser degrees of prematurity, suggesting that 11 beta OH activity may be regulated during fetal development to increase during the latter part of gestation.

Standard Versus Hyperimmune Intravenous Immunoglobulin in Preventing or Treating Neonatal Bacterial Infections

Although current studies suggest that IVIg is safe, larger controlled trials will soon be published and will be important to confirm this observation. In addition, the current studies do not establish the efficacy of IVIg for either treating or preventing neonatal bacterial infections. Some studies with small numbers of infants suggest benefit of IVIg therapy and prophylaxis; however, the studies reviewed do not, individually or combined, prove efficacy. Clinicians and investigators must not confuse studies that prevent infection with those that treat infection because different therapeutic regimens may be necessary. Many questions remain concerning IVIg therapy, such as is IVIg efficacious in preventing or treating neonatal sepsis, what is the appropriate immunoglobulin dosage, and how variable is the pathogen-specific antibody activity of standard IVIg products. To determine the appropriate use of IVIg in neonates effectively, well-designed and carefully controlled trials are needed to address these issues using sufficiently large numbers of infants to arrive at valid scientific conclusions. Although many questions will be answered with the trials currently in progress, we must continue to base further recommendations for immunoglobulin therapy on solid scientific data.

Ontogeny of Hepatic Type I Insulin-Like Growth Factor Receptors in the Rat

We studied the pre- and postnatal developmental regulation of the hepatic type I IGF receptor in the rat. Fetal rat liver membranes bound IGF-I throughout the latter part of gestation (d 17 to 21). After birth, binding diminished rapidly, reaching barely detectable levels by the 13th postnatal d. However, the presence of type I IGF receptors was readily demonstrated by affinity-labeling throughout the immediate postnatal period and in adult rats. Furthermore, IGF-I-dependent autophosphorylation of type I receptors could be seen in both fetal and adult liver membranes. Fasting for 48 h in adult rats led to a 2- to 3-fold increase in affinity-labeled type I IGF receptors. In contrast, nutrient deprivation to the fetus, via maternal fasting, did not alter fetal hepatic IGF-I binding or affinity-labeling of the type I receptor. These results support a role for the IGF and the type I IGF receptor in the autocrine/paracrine regulation of hepatic growth through the latter stages of gestation in the rat. The demonstration of enzymatically active type I IGF receptors in adult liver, and their increased expression in fasted adult rats is consistent with an autocrine/paracrine role for hepatic IGF-I in the adult.

Cis-acting sequences from a human surfactant protein gene confer pulmonary-specific gene expression in transgenic mice.

Pulmonary surfactant is produced in late gestation by developing type II epithelial cells lining the alveolar epithelium of the lung. Lack of surfactant at birth is associated with respiratory distress syndrome in premature infants. Surfactant protein C (SP-C) is a highly hydrophobic peptide isolated from pulmonary tissue that enhances the biophysical activity of surfactant phospholipids. Like surfactant phospholipid, SP-C is produced by epithelial cells in the distal respiratory epithelium, and its expression increases during the latter part of gestation. A chimeric gene containing 3.6 kilobases of the promoter and 5'-flanking sequences of the human SP-C gene was used to express diphtheria toxin A. The SP-C-diphtheria toxin A fusion gene was injected into fertilized mouse eggs to produce transgenic mice. Affected mice developed respiratory failure in the immediate postnatal period. Morphologic analysis of lungs from affected pups showed variable but severe cellular injury confined to pulmonary tissues. Ultrastructural changes consistent with cell death and injury were prominent in the distal respiratory epithelium. Proximal components of the tracheobronchial tree were not severely affected. Transgenic animals were of normal size at birth, and structural abnormalities were not detected in nonpulmonary tissues. Lung-specific diphtheria toxin A expression controlled by the human SP-C gene injured type II epithelial cells and caused extensive necrosis of the distal respiratory epithelium. The absence of type I epithelial cells in the most severely affected transgenic animals supports the concept that developing type II cells serve as precursors to type I epithelial cells.

PGF2 alpha and PGE2 binding to rat myometrium during gestation, parturition, and postpartum

The specific binding of prostaglandins (PG) F2 alpha and E2 was studied in a rat myometrial membrane-enriched fraction during the latter part of gestation and parturition, as well as in the postpartal period. Tritiated PGE2 and PGF2 alpha binding was specific, saturable, time dependent, and directly proportional to the amount of membrane protein. Scatchard analysis indicated the presence of high-affinity (Kd2) and low-affinity (Kd2) binding sites for both PGs. The affinity of both binding sites for PGF2 alpha and the apparent Kd2 for PGE2 remained essentially the same throughout gestation and post-partially and were similar to nonpregnant rats. The apparent Kd1 of PGE2, however, increased by 10-fold from day 21 of gestation to 1 day postpartum. Although the maximal binding capacity of the high-affinity (Bmax1) and low-affinity (Bmax2) binding sites of PGF2 alpha showed a nonsignificant increase compared with prepartum values, reaching maximal values 12-24 h postpartum, those of PGE2 showed a significant increase on the third day after delivery. The concentration of prostanoids in uterine venous plasma and amniotic fluid increased significantly with approaching parturition, whereas plasma progesterone decreased, raising the estradiol-progesterone ratio 25-fold. After unilateral fetectomy, the binding sites for PGF2 alpha and PGE2 increased significantly compared with the contralateral pregnant horns. Administration of the PG synthetase inhibitor, indomethacin, also increased two- to threefold both PGF2 alpha and PGE2 binding compared with the placebo group, whereas intrauterine administration of PGF2 alpha and PGE2 significantly reduced it.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunological responses to bovine virus diarrhoea virus infections

Infection of normal calves with bovine virus diarrhoea virus (BVDV) is a transient self-limiting infection that can result in a period of immunosuppression. The virus appears to be able to replicate in all of the major lymphocyte sub-populations as well as in accessory cells. This may result in the leukopenia that is often a sequel of infection and affects B-cells as well as the T-cell sub-populations expressing either BoCD4 or BoCD8 antigens. B and T-cell responses are affected as a consequence of exposure to BVDV and there is a reduced ability to control other infections. Evidence is summarised and shows that immunoglobulin is an important mediator of immunity to infection with BVDV. Although the foetus can mount an immune response in the latter part of gestation, during the first trimester it does not. A specific state of tolerance is induced and this is associated with change in the proportion of certain lymphocyte sub-populations and ability to respond to immune stimulation.

Epidermal growth factor receptors in rat placenta, amnion and yolk sac: characteristics of specific binding are dependent on gestational age.

Studies of [125I]-EGF binding to the rat placenta, amnion and yolk sac were carried out on days 14, 17 and 20 of gestation. In the placenta EGF binding was detectable on all 3 days; in the amnion EGF binding was undetectably low on day 14 but was present on days 17 and 20, while in the yolk sac EGF binding was undetectably low on all 3 days. Although Scatchard analysis of EGF binding to placental tissue raised the possibility of high and low affinity receptors, a statistical analysis of the ligand binding data was consistent with the presence of only one type of EGF receptor. The overall affinity of the receptors did not change with stage of gestation. However, the concentration of EGF receptors was lower in placental tissue on day 17 than on days 14 or 20 of gestation; the receptor concentrations were similar on days 14 and 20. It is suggested that EGF binding to the placenta, amnion, and yolk sac may reflect the levels of cell proliferation in those tissues in the latter part of gestation.

The role of gastrin in the development of the gastrointestinal tract in fetal sheep.

We have investigated the role of gastrin in the development of the gastrointestinal tract during the latter part of gestation in fetal sheep. We surgically removed the major source of gastrin, the gastric (abomasal) antrum, from five fetuses at 90 days of gestation. The remaining abomasum was anastomosed to the pylorus allowing unobstructed flow of luminal contents. Another five fetuses, subjected to sham-antrectomies at 90 days, served as controls. Further surgery was performed in all fetuses at 120 days for the placement of vascular catheters to permit measurement of plasma gastrin concentrations. The fetuses were infused with [3H]thymidine to study villus cell migration rates. At 135 days of gestation samples of gastric (abomasal) fundus, and proximal and distal small intestine, were processed for histology and morphometric analysis. The antrectomized fetuses had significantly lowered plasma gastrin concentrations (P less than 0.025) between 120 and 135 days. At 135 days, the mean body weight, crown-rump length, total gut weight and small intestinal weight and length were not significantly different between the two groups. Similarly, there were no significant differences between groups in the mean thicknesses of the gut wall, mucosa and muscularis externa, or in the mean villus height and crypt depth in the proximal or distal parts of the small intestine. Villus cell migration rate in the proximal and distal small intestine was not affected by antrectomy. No simple relationship could be demonstrated between any of these parameters and plasma gastrin concentration. In the antrectomized fetuses, the mean crypt density and crypt-to-villus ratio were significantly reduced in the proximal small intestine (P less than 0.05), while only the density of villi was reduced in the distal small intestine (P less than 0.05). In the antrectomized fetuses there were significant correlations between plasma gastrin and the fraction of fundic mucosa occupied by gland and pit (P less than 0.005), and between plasma gastrin concentration and villus density (P less than 0.01) and crypt-to-villus ratio (P less than 0.025) in the proximal small intestine. In the sham group these correlations were absent. We conclude that the removal of the gastric antrum in fetal sheep results in decreased plasma gastrin concentration, and that gastrin appears to have a regulatory or trophic role on the gut mucosa in these circumstances.(ABSTRACT TRUNCATED AT 400 WORDS)

Preprocorticotropin releasing hormone: cDNA sequence and in vitro processing

Human corticotropin releasing hormone (hCRH) is expressed in both hypothalamus and placenta. Its expression in placenta increases markedly in the latter part of gestation. We have isolated and characterized a human placental CRH cDNA clone and performed in vitro translation of sense-strand hCRH cRNA synthesized from this cDNA and co-translational processing of the resulting preproCRH peptide. Sequence analysis of the cDNA confirms the exon-intron junctions predicted from the gene sequence and establishes the presence of at least two sites of transcription initiation of the human CRH gene in placenta. The translated preproCRH gene product contains a hydrophobic, functional signal sequence which suggests that placental CRH peptide is capable of being secreted. These structural features of the preproCRH mRNA and peptide may help to understand the regulation of placental CRH observed during human gestation.

Influence of Maternal Plasma Protein Binding on Fetal Unbound Plasma Concentration of Propranolol in the Pregnant Ewe

According to theory, for a drug of nonrestrictive, flow-limited clearance, a change during pregnancy of the unbound fraction (fu) of drug in maternal plasma should cause a change in steady-state unbound plasma drug concentration (Cu) in maternal plasma, which should also cause a change in fetal Cu. This theory was examined In 14 chronically cannulated, unanesthetized pregnant ewes in which 28 separate experiments were performed during the latter part of gestation. An initial bolus dose and 3-h constant rate infusion of propranolol were administered via the maternal jugular vein and steady-state maternal and fetal carotid arterial plasma total and unbound propranolol concentrations were measured. Fetal Cu (32 ± 21 ng/mL) was significantly less than maternal Cu(78 ± 52 ng/mL), due to previously demonstrated fetal hepatic extraction of propranolol. Notwithstanding fetal elimination, there was a significant correlation between fetal Cu and maternal Cu (r = 0.41, p < 0.025). There was also a strong correlation between fetal Cu and the maternal unbound fraction of drug (fu r = 0.75, p < 0.001). We conclude that for propranolol, a drug of nonrestrictive, flow-limited clearance, changes in maternal fu can have a significant influence on fetal Cu and therefore would be expected to influence the pharmacological effect of the drug in the fetus.

Haemopoietic development in the foetal lamb from 85-135 days measured by (3H)-thymidine incorporation in vitro.

Cell suspensions from the bone marrow (BM), spleen, thymus, liver and lymph nodes of 14 foetal lambs from 85-135 days gestation were incubated in vitro with 3H-thymidine (TdR). Cells from the long bones, the humerus, tibia and femur, yielded similar results, viz., the total leucocyte population of the bone increased from a mean of 8.8 X 10(6) at 85-90 days (N = 4) to a mean of 487 X 10(6) at 130-135 days (N = 3); the rate of incorporation of TdR varied from 22,460-45,960 c.p.m./h/10(6) cells with no clear trend related to foetal age; this rate is consistent with active mitosis occurring in the expanding BM cell population; bone weight and cell number/bone increased in parallel, and the total mitotic capacity of the bone showed a similar pattern. In the liver, spleen and thymus the incorporation of TdR per 10(6) cells decreased during the latter part of gestation. Despite growth of the liver (from 18 g to 71 g), the number of white blood cells (WBC) extracted from this tissue was lower at 135 days than at 85 days, suggesting that the haemopoietic capacity of the liver declined during this period. The marked increase in total WBC numbers in the thymus suggests this tissue may be supplying circulating lymphocytes to the growing foetus.

Synthesis of chain elongated-desaturated fatty acids from palmitic acid by liver and brain microsomes during the development of the pig

1. 1. Rates of chain elongation-desaturation of C 16:0 were compared for liver and brain microsomes in fetal, neonatal and postnatal piglets. 2. 2. Rates of chain elongation of C 16:0 were greatest in liver in the postnatal period. 3. 3. For all developmental periods examined, the amount of chain elongated fatty acid of C 20 or greater chain length exceeded the amount of C 18 precursors synthesized from C 16:0. 4. 4. These observations suggest that chain elongation of fatty acids occurs during the latter part of gestation at rates equivalent to that observed in the early postnatal period.

Development of angiotensin converting enzyme in fetal lung and placenta of the rat and human.

Angiotensin converting enzyme (ACE) activity in fetal lung and placenta was determined by the method of Cushman and Cheung (1971) during the second trimester of human pregnancy and throughout the rat gestation. The enzyme activity in the neonatal rat lung was also determined during the first 19 days of life. The enzyme activity in both tissues of both species increased with gestation. The activity in human fetal lung at the end of the second trimester was already 70% of that present in the adult human lung while rat fetal lung enzyme activity at term was only 15% of the adult value. The activity in the term placenta of the human and rat was respectively 13% and 5% that of the adult lung value. Developmental increases in enzyme activity continued in the neonatal rat lung till adult value at about 19 days postpartum. The pattern of fetal lung enzyme development in the rat resembled that of the rabbit fetal lung as determined by other investigators using different techniques but was different from that of the human. The findings support the suggestion that ACE in the lung and placenta play important roles in the maintenance of circulatory homeostasis during the latter part of gestation, at birth and early postpartum, albeit at a different extent in different species.

Somatomedins and insulin in diabetic pregnancies: effects on fetal macrosomia in the human and rhesus monkey.

The concentrations of the somatomedins (SMs) insulin-like growth factors I and II (SM-C/IGF-I and IGF-II) were measured by RIA in six normal and seven insulin-dependent diabetic pregnant women and their infants at delivery. SM-C/IGF-I and IGF-II levels in the two groups of women were similar. Maternal IGF-II concentrations correlated with maternal hemoglobin AIc levels (r = 0.68) and infant birth weight ratios (actual birth weight/expected 50th percentile sex-corrected birth weight for gestation age; r = 0.54). SMC/IGF-I and IGF-II levels in umbilical plasma in infants of diabetic mothers did not differ from those in control infants, but were lower than the corresponding maternal values. In contrast, umbilical plasma levels of C-peptide immunoreactivity were significantly elevated in the infants of diabetic mothers (2.25 +/- 1.85 (+/-SD) vs. 0.34 +/- 0.15 pmol/ml; P less than 0.01). The infant birth weight ratio was logarithmically correlated with the umbilical plasma C-peptide immunoreactivity (r = 0.78). SM levels were also measured by radioreceptor assay in five normal and five hyperinsulinemic rhesus monkey fetuses. When chronic hyperinsulinemia was produced by continuous SC infusion of insulin in the fetal rhesus monkey, the fetal birth weight ratio was also found to be logarithmically correlated with the fetal plasma insulin concentration (r = 0.81). The fetal SM peptide content was elevated only in the fetuses with plasma insulin levels greater than 3000 microU/ml. The fetal weight gains in response to hyperinsulinemia in the human and rhesus are similar. Since fetal SM levels in the humans and monkeys were not significantly different in the two groups, our data suggest that insulin plays the predominant role in stimulating human and subhuman primate excess fetal weight gain of the infant of the diabetic mother during the latter part of gestation.

Hypercholesterolemia due to elevated low density lipoprotein-cholesterol in newborns with anencephaly and adrenal atrophy.

In the present investigation, we evaluated the relationship between plasma lipoprotein-cholesterol and adrenal steroid production in abortuses and newborns in whom the adrenal was expected to be atrophic, i.e. in anencephalics. We found that umbilical cord plasma levels of dehydroepiandrosterone sulfate (DS) in 23 anencephalics delivered between 13.5 and 45.5 weeks of gestation (mean +/- SE, 176 +/- 37 ng/ml) were significantly lower than those in normal newborns of similar gestational ages; the umbilical cord plasma concentrations of cortisol in many anencephalics, however, were within normal limits. The levels of total cholesterol (134 +/- 10 mg/dl) and low density lipoprotein (LDL)-cholesterol (94 +/- 8 mg/dl) were substantially higher (up to 4-fold) in umbilical cord plasma of anencephalics than in umbilical cord plasma of normal newborns. The mean level of high density lipoprotein-cholesterol in umbilical cord plasma of anencephalic abortuses and newborns (38 +/- 4 mg/dl) was approximately 50% higher than that in normal newborns. The lowest plasma cholesterol level (56 mg/dl) and a concentration of DS (480 ng/ml) that was among the highest seen in the group of anencephalics were found in an anencephalic newborn in whom adrenals were of near-normal weight. Plasma cholesterol levels were inversely correlated to adrenal weights and plasma DS levels, and plasma DS levels were correlated to adrenal weight. Whereas the estimated plasma pool of DS in normal newborns increased to over 300 micrograms during the latter part of gestation, that of anencephalic newborns was much lower (less than 1 to 26 micrograms) and did not appear to increase as a function of gestational age. Conversely, the estimated plasma pool of cholesterol in normal newborns appeared to decline slightly during the last 10 weeks of gestation (80 mg at term), whereas that of anencephalic newborns expanded greatly near term; levels (approximately 200 mg) were attained that were about 3 times those in normal newborns. We conclude that the hypercholesterolemia in anencephalic newborns, due primarily to extremely elevated plasma levels of LDL-cholesterol, is a result of decreased uptake and utilization of plasma LDL-cholesterol for steroid biosynthesis by the adrenals. Since hypercholesterolemia is apparently early in gestation in anencephalic abortuses, we speculate that in normally developing fetuses, plasma LDL-cholesterol is used as substrate for adrenal steroidogenesis early in gestation as well as near term when the rates of growth and steroid production by the adrenals accelerate markedly.

Effects of antibodies to nerve growth factor on intrauterine development of derivatives of cranial neural crest and placode in the guinea pig

Fetal guinea pigs transplacentally exposed to maternal nerve growth factor antibodies in the latter part of gestation show marked depletion of sensory neurons in the trigeminal ganglion. Sensory neurons of the nodose ganglion and spiral ganglion which are derived from placodes, and parasympathetic motor neurons of the ciliary, otic, and sphenopalatine ganglia which are derived, like the bulk of the trigeminal ganglion, from cranial neural crest, are unaffected by the antibodies. Previous studies showed that sensory and some sympathetic derivatives of spinal neural crest are effected but that more peripherally located structures of similar origin are not. The local microenvironment in the fetus appears to alter the NGF requirements of structures derived from the same primordia. The model described provides a useful means of studying the effect of trophic factor inhibition in the natural fetal setting and is free of many potential artifacts of tissue culture. Comparison of the animal results with the pathology of familial dysautonomia indicates that nerve growth factor dysfunction alone does not, in our current state of knowledge, adequately account for the etiology of the disease.

Placental transport of the non-metabolisable alpha-aminoisobutyric acid in guinea-pigs given a commercial chlorobiphenyl preparation or a defined, pure chlorobiphenyl.

The placental transfer of the non-metabolisable alpha-aminoisobutyric acid was studied by means of a perfusion technique in pregnant guinea-pigs given the commercial chlorobiphenyl preparation, Clophen A50 (C-A50) or pure 2,2',4,4',5,5'-hexachlorobiphenyl (HCB), during different periods of gestation. It was shown that a total dose of 30 mg of HCB given during the latter part of gestation (day 45 to 61) decreased amino acid transport, while 30 mg of C-A50 did not. At a dose of 30 mg daily given from day 28 to day 61, again only HCB decreased the amino acid transfer. An amount of 60 mg C-A50 was required to reduce this transport. The concentration of the amino acid in blood from foetuses remaining in the uterus was significantly increased when the dams were given 60 mg of C-A50, indicating a reduced foetal uptake of the amino acid. It is suggested that the decreased placental transfer of the amino acid is dependent on physio-chemical interactions (e.g. caused by hydrophobic properties) between the chlorobiphenyls and the NaK-ATPase enzyme complex which is involved in amino acid transport.

Alveolar lavage and lavaged lung tissue phosphatidylcholine composition during fetal rabbit development.

Pulmonary surfactant, the major surface-active component of which in the adult is dipalmitoylglycerophosphocholine, can be obtained by lavaging lungs with physiological saline. We have previously shown that there is an increase in the amount of phosphatidylcholine in fetal rabbit lung lavage during the latter part of gestation. We have now measured the amount of disaturated phosphatidylcholine as well as the fatty acid composition of phosphatidylcholine in lung lavage from fetal rabbits during the period 27 days' gestation to full term (31 days). There was no developmental change in the amount of disaturated phosphatidylcholine during the period examined. About 50% of the total phosphatidylcholine was disaturated which is approximately the same as in adult rabbit lung lavage. The fatty acid composition, however, did change. There was an increase in the amount of 16:0 from about 20% of the total fatty acids in phosphatidylcholine at 27-28 days to about 60% at full term, after birth, and in the adults. There was a corresponding decrease in the amounts of 14:0, 18:0, and longer chain fatty acids, most of which were saturated. In the lavaged lung tissue, there was a 2.6-fold increase in the percentage of phosphatidylcholine which was disaturated during the period 27-31 days' gestation. It had not decrease to the adult value 24 hr after birth.

Regulation of fetal lung phosphatidyl choline synthesis by cortisol: role of glycogen and glucose.

Twenty pregnant rabbits were studied in pairs. Half were given cortisol subcutaneously on days 24, 25, and 26 of gestation in dosage of 2 mg/kg/day. Half served as controls and received saline. The fetal lungs were studied on the 27th day of gestation by incubating lung slices in the presence of [6-14C]glucose. Glucose consumption significantly increased in the tissue from animals treated with cortisol, 17.61 "/- 5.56 (SD) mumol/g in the controls (P less than 0.05). The glycogen content of tissue treated with cortisol was significantly reduced compared to the controls, 2.42 +/- 0.97 (SD) mg/g wet lung versus 3.81 +/- 1.05 (SD) mg/g (P less than 0.05). Treatment with cortisol resulted in significantly enhanced incorporation of the 14C label into glycogen and phosphatidyl choline (Tables 3 and 4). These data suggest that glucocorticoids affect fetal lung phosphatidyl choline production by promoting glycogenolysis and increasing glucose incorporation into phosphatidyl choline.

Stimulation of adrogen biosynthesis in rat fetal testes in vitro by gonadotropins.

Rt fetal testes in the latter part of gestation (Days 17-21) have enzyme systems for the de novo synthesis of androgen. Under the conditions of these in vitro experiments the major androgen produced was testosterone, with lesser amounts of androstenedione and 5n-dihydrotestosterone. As little as 10 m IU of hCG added in vitro significantly increased androgen synthesis in the fetal testis on Day 19. Bovine, ovine or human LH but not bovine or ovine FSH also stimulated the synthesis of androgens by the rat fetal testis. The synthesis of testosterone was increased by the addition of precursors: 15-fold by the addition of pregnenolone, 20-fold by progesterone, and 47-fold by dehydroepiandrosterone. However, the increase was marginal in the presence of sulfates of pregnenolone or dehydroepi- androsterone. These results suggest that �5-isomerase-3�3-hydroxysteroid dehydrogenase and 1 713-hydroxysteroid dehydrogenase are active in the fetal testes; in contrast, the activity of steroid sulfatase was relatively low.