High concentrations of plasma immunoreactive inhibin during normal pregnancy in women

The plasma inhibin concentrations in 190 normal pregnant women at 5-40 weeks gestation and in 4 puerperal women were measured by a specific RIA for human inhibin. The average plasma inhibin concentrations in pregnant women throughout pregnancy (minimum, 2.25 +/- 0.48 IU/mL at 17 weeks gestation; maximum, 24.15 +/- 6.99 IU/mL at 39 weeks gestation) were much higher than those in nonpregnant women with a normal menstrual cycle (0.46 +/- 0.04 IU/mL in the midfollicular phase and 2.02 +/- 0.47 IU/mL in the midluteal phase). The inhibin concentrations were already high at 5 weeks gestation (7.54 +/- 1.10 IU/mL) and rose to peak at 8-10 weeks gestation. The concentrations then decreased and remained relatively low during 14-30 weeks gestation, but rose again during the third trimester. The inhibin concentrations decreased to undetectable levels after delivery. Immunoreactive inhibin was demonstrated in the corpus luteum and term placental extracts, and the dose-response curves were parallel to an inhibin preparation from human follicular fluid. Immunoreactive inhibin concentrations were also high in both the umbilical vein and artery (7.77 +/- 0.80 and 7.84 +/- 0.78 IU/mL, respectively). These observations suggest that both the corpus luteum and placenta are likely sources of inhibin.     

THE MATERNAL OVARY IS NOT THE SOURCE OF CIRCULATING INHIBIN LEVELS DURING HUMAN PREGNANCY

The concentration of immunoreactive inhibin in serum was measured in three pregnant women with premature ovarian failure involved in a donor oocyte in-vitro fertilization programme. Inhibin was not detectable in peripheral serum prior to conception but rose within 2-4 weeks of embryo transfer, whereafter levels rose gradually during pregnancy (less than 20 weeks 1.22 U/ml (0.85-1.76) versus greater than 20 weeks 2.28 U/ml (1.42-3.67), P less than 0.01; geometric mean +/- 67% confidence interval) and were similar to those observed in 24 normal pregnant women. hCG rose in parallel with inhibin during early gestation, but declined after 3 months. FSH levels were elevated before conception and were suppressed during pregnancy. In conclusion (i) immunoreactive inhibin is detectable from early gestation in women with no endogenous ovarian function indicating that the maternal ovary does not contribute significantly to inhibin secretion during pregnancy; (ii) the trophoblast is the likely source of inhibin during pregnancy; (iii) the regulation of hCG and inhibin secretion differs throughout gestation; and (iv) inhibin may have a role in FSH regulation during pregnancy and/or a local role within the feto-placental unit.     

Oestrone, oestradiol-17beta and oestriol levels in human foetal plasma during gestation and at term

Marked rises in both unconjugated and sulphoconjugated estrone, estradiol-17-beta and estriol were observed in human fetal plasma between midgestation and term. Significant arterio-venous differences were found in the umbilical cord plasma. No consistent arterio-venous differences were found in the umbilical cord plasma. This indicates that all 3 estrogens are secreted from the placenta into the fetal circulation in the unconjugated form. Mean unconjugated estrogen (estrone + estradiol-17-beta + estriol) levels rose from 22.7 ng/ml at 17-20 weeks of gestation to 108.9 ng/ml at term in umbilical venous plasma and from 4.3 ng/ml to 23.3 ng/ml in umbilical arterial plasma. This represents a secretion rate of approximately 30 mg estrogen/day into the umbilical vein at term. Mean estrogen sulphate levels rose from 128 ng/ml to 313 ng/ml in the cord plasma during the same period. Of the 3 estrogens measured, estriol was quantitatively the major estrogen in fetal plasma. It consistently represented about 78% of the unconjugated fraction and 95% of the sulphate fraction at all stages of gestation. The method of delivery did not have a significant effect on the estrogen levels in uncomplicated pregnancies. Similar estrogen levels were found in fetal heart blood after either hysterotomy at spontaneous abortion at 16-20 weeks of gestation, and no significant differences were found for estrogen levels in cord plasma after elective Caesarean section at 38-39 weeks when compared with estrogen levels after normal delivery at term. A significant rise in fetal unconjugated estrogens at a time when fetal corticosteroids are increasing may be of physiological importance for fetal maturation in women.     

Studies on human sexual development. III. Fetal pituitary and serum, and amniotic fluid concentrations of LH, CG, and FSH.

Fetal sera (9-20 weeks fetal age, n = 80) and pituitary glands (9.5-20 weeks, n = 36) obtained from hysterotomy specimens, and amniotic fluids (amniocentesis; 8-40 weeks, n = 123) were assayed for FSH, LH (betaLH assay) and CG (betaCG assay). Results are expressed as mass of pure hormone. Prior to 12 weeks fetal age, pituitary, serum and amniotic fluid concentrations of LH and FSH were low or unmeasurable. In contrast, levels of CG in serum and in amniotic fluid were clearly measurable prior to 12 weeks. There was a definite CG peak at 11-14 weeks with levels up to 550 ng/ml in serum and 7400 ng/ml in amniotic fluid. Although LH levels began to rise at 12 weeks, when CG levels started to decline, serum levels of LH from 14-20 weeks in males (2-13 ng/ml) were still lower than the majority of CG levels at this time (6-115 ng/ml). These observations suggest that CG is the primary stimulus to the fetal Leydig cell which results in testosterone secretion (peak 11-17 weeks) and masculine differentiation of the genital tract. Significantly lower concentrations of both FSH and LH were observed in pituitary, serum and amniotic fluid between 12-20 weeks fetal age in males compared to females. This may be a result of feedback inhibition by the higher concentrations of testosterone in males at this time. Amniotic fluid FSH and LH concentrations correlated with their respective serum and pituitary values (P less than 0.01) indicating that amniotic fluid may provide a convenient index of fetal serum concentrations.     

Plasma 20 alpha-dihydroprogesterone, progesterone and 17-hydroxyprogesterone in normal human pregnancy

The peripheral plasma levels of 20alpha-dihydroprogesterone (20alpha-DHP), progesterone (P) and 17-hydroxyprogesterone (17-OHP) were measured by radioimmunoassay techniques in 440 samples during normal human pregnancy between weeks 4 and 41. The levels of 20alpha--DHP in plasma from the 4th to the 6th week were between 6.0 and 6.6 ng/ml. From then until the 21st week the average plasma 20alpha-DHP concentrations remained at the same level between 4.0 and 6.3 ng/ml; they then rose significantly to and beyond term, levels reaching over 40 ng/ml. The range of mean plasma concentration of P during the first trimester of pregnancy fell to a nadir in the 9th week (170 ng/ml) then rose with increased gestation until the 39th week (190.4 ng/ml) followed by a slight and not significant drop. Single measurements of plasma 17--OHP from the 4th to the 6th week of pregnancy gave value between 2.8 and 3.6 ng/ml, but from the 7th week the mean plasma 17--OHP levels gradually declined, then from week 30 the 17-OHP concentration increased to reach a mean level of 7.63 ng/ml in the 41st week. The ratio P/20alpha--DHP increased from the 4th (3.5:1) to the 24th week (15.6:1) and then decreased from 25th week (7.9:1) towards term (3.2:1).     

AMNIOTIC FLUID CONCENTRATIONS OF 3,3'',5''-TRI-IODOTHYRONINE (REVERSE T3), 3,3''-DI-IODOTHYRONINE, 3,5,3''-TRI-IODOTHYRONINE (T3) AND THYROXINE (T4) IN NORMAL AND COMPLICATED PREGNANCY

Amniotic fluid concentrations of 3,3',5'-tri-iodothyronine (rT3), 3,3'-Di-iodothyronine (3,3'-T2), 3,5,3'-tri-iodothyronine (T3) and T4 were studied in 384 women during normal and complicated pregnancy. An inverse correlation was observed between decreasing rT3 and increasing 3,3'-T2 concentrations in amniotic fluid with gestational age. The mean rT3 level in normal pregnancy was 2.81 nmol/1 at 12-20 weeks and decreased significantly to 1.06 nmol/1 at 36-42 weeks of gestation. The mean 3,3'-T2 concentration was 49.1 pmol/1 at12-20 weeks increasing to 119 pmol/1 at 36-42 weeks. The mean T4 value of 3.83 nmol/1 at 12-20 weeks was about half that of later periods. The T3 concentration in a random sample of 45 amniotic fluids ranged from less than 28 to 370 pmol/1 (mean 102 pmol/1). The mean rT3, 3,3'-T2 and T4 values measured in patients with intra-uterine malnutrition, gestation diabetes, tocolysis, placental insufficiency and rhesus incompatibility at 31-40 weeks of gestation were not significantly different from those in uncomplicated pregnancy. Significantly decreased rT3 and T4 concentrations were found in toxaemia. From the results obtained in complicated pregnancy it may be concluded that measurements of iodothyronines, especially rT3, in amniotic fluid have insignificant diagnostic value in the recognition of intra-uterine lesions with the probable exception of fetal hypothyroidism. The analysis of the dependence of iodothyronine concentrations on the gestational age showed a maximum of rT3 and T4 levels between 20 and 30 weeks of pregnancy. This marked rise of iodothyronine concentrations in amniotic fluid at mid-gestation may be due to the onsetting maturation of the hypothalamic-pituitary-thyroid control system of the fetus.     

Human fetal adenohypophysis: morphologic and functional analysis in vitro.

Pituitaries from 24 human fetuses at 7-20 weeks of gestation were studied in culture to assess hormone release, response to adenohypophysiotropic hormones and cytodifferentiation by electron microscopy in cultures lasting 4-8 days and in some cases up to 28 days. At 7 weeks of gestation, ACTH was released by cultured cells which included recognizable corticotrophs. GH was released by cells cultured from 8- to 9-week fetuses and densely granulated somatotrophs were present in the cultures. alpha-Subunit of glycoprotein hormones was present in cultures from 10-week fetuses and TSH and LH were released from 12-week fetuses. FSH was found in cultures of a 13-week female fetus but not before 14 weeks in cultures from males. The levels of FSH and LH were higher in media from cultures of females than from those of males at all ages from detection to 20 weeks, whereas alpha-subunit was slightly higher in media from males. While cells with features of the glycoprotein hormone cell line were found in cultures from 10-week fetuses, no characteristic thyrotrophs or gonadotrophs were recognized. PRL was not measured in basal incubations before 14 weeks. The amounts of all hormones released were proportional to fetal age and decreased with duration of culture. Cortisol suppressed ACTH release in cultures from 7- to 8-week fetuses. Responsiveness of GH release to GRH/SRIH, of ACTH to CRH, and of FSH to GnRH, was found at 12 weeks; LH stimulation by GnRH and TSH response to TRH were documented at 14 weeks. Increments of gonadotropin release during incubation with GnRH were greater in cultures from females than in those from males. PRL release responded to GRH stimulation and to SRIH inhibition in parallel with GH; this behavior is consistent with production of both hormones by mammosomatotrophs. The onset of hormone release by cultured human fetal pituitaries correlates with the detection of hormones biochemically and immunohistochemically. Responsiveness of fetal adenohypophysial cells to hormonal influences indicates functional maturity early in gestation.     

Amniotic fluid concentrations of dimeric inhibins, activin A and follistatin in pregnancy

OBJECTIVE: The feto-placental unit is the major source of circulating concentrations of inhibin A and activin A in human pregnancy. The aim of this study was to measure the amniotic fluid concentrations of inhibin A, inhibin B, activin A and follistatin in pregnancies bearing male and female fetuses. DESIGN AND METHOD: Amniotic fluid samples collected by amniocentesis were stored at -20 degrees C. Dimeric inhibins, 'total' activin A and 'total' follistatin were measured using specific two-site enzyme immunoassays. Samples were assayed blindly and the information on fetal sex was obtained from the cytogenetics laboratory. RESULTS: Data show that amniotic fluid concentrations of inhibin A, inhibin B and activin A gradually increase with gestation whilst concentrations of follistatin are similar between weeks 15 and 20 of pregnancy. Mean amniotic fluid levels of inhibin A and inhibin B at 16 and 17 weeks gestation and mean activin A levels at 15 and 16 weeks gestation are considerably lower in pregnancies with male (n=24) compared with female (n=28) fetuses. Levels of follistatin are not different in the male and female fetal pregnancies at any studied gestation. CONCLUSIONS: The results indicate that amniotic fluid contains high concentrations of inhibins (A and B), activin A and follistatin in early pregnancy suggesting that these hormones are produced by the fetal membranes and may be involved in the development of the fetus.     

Longitudinal study of progestins, mineralocorticoids, and glucocorticoids throughout human pregnancy

The maternal adrenal cortex seems to be involved in the adaptation to pregnancy. To study in detail adrenocortical secretion during pregnancy, we measured plasma aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, and cortisone simultaneously by RIA after extraction and automated Sephadex LH-20 chromatography of 10 normal pregnant women longitudinally throughout pregnancy at weeks 8-10, 14-17, 21-24, 28-32, and 38 as well as at the time of admission to the delivery room. The mean plasma progesterone and 17-hydroxy-progesterone concentrations increased from 37.2 +/- 6.5 (+/- SE) and 8.2 +/- 1.0 nmol/L, respectively, in early gestation to maximum levels of 138.0 +/- 25.7 and 22.8 +/- 2.2 nmol/L at week 38 (P less than 0.01). Plasma glucocorticoid levels rose 2- to 3-fold (P less than 0.01) from weeks 8-10 (corticosterone, 18.5 +/- 5.4; 11-deoxycortisol, 1.9 +/- 0.2; cortisone, 24.2 +/- 4.2; cortisol, 195.5 +/- 37.6 nmol/L) to week 38 (corticosterone, 42.9 +/- 11.2; 11-deoxycortisol, 4.6 +/- 0.5; cortisone, 71.5 +/- 13.6; cortisol, 420 +/- 63 nmol/L). Similarly, plasma mineralocorticoid levels increased 5- to 7-fold (P less than 0.01) from weeks 8-10 (11-deoxycorticosterone, 0.69 +/- 0.12; aldosterone, 0.41 +/- 0.08 nmol/L) to maximum levels at week 38 (5.3 +/- 0.9 and 2.1 +/- 0.3 nmol/L, respectively). At the time of admission to the delivery room, plasma 11-deoxycortisol, corticosterone, and cortisol concentrations were higher (P less than 0.02) than at 38 weeks, but plasma progestin and mineralocorticoid concentrations were not. We conclude that the source of the elevated maternal corticosteroid levels in pregnancy in addition to the estrogen-mediated rise in corticosteroid-binding globulin is the maternal adrenal cortex itself. The peak glucocorticoid levels at admission to the delivery room reflect increased maternal and fetal stress with the onset of labor.     

Amniotic fluid androgens and estrogens in midgestation.

Amniotic fluid androgen and estrogen levels associated with 48 male and 72 female fetuses between 14 and 20 weeks of gestation were measured. Amniotic fluid testosterone levels were significantly higher (P less than 0.001) in the male (224 +/- 11 pg/ml) than the female fetuses (39 +/- 2 pg/ml) with no overlap of values. Amniotic fluid androstenedione concentrations were also significantly higher (P less than 0.001) with male (1024 +/- 53 pg/ml) than female fetuses (668 +/- 39 pg/ml), but there was overlap. There was no difference between anmiotic fluid dehydroepiandrosterone levels for the two sexes. Estrone concentrations were slightly but not significantly higher with the male (353 +/- 33 pg/ml) than with female fetuses (331 +/- 28 pg/ml), while estradiol concentrations were significantly higher (P =0.002) with the female (96 +/- 8 pg/ml) than male (64 +/- 4 pg/ml) fetuses. It is interpreted that the higher amniotic fluid testosterone and androstenedione levels for the male fetuses reflect fetal testicular secretion. The significantly higher estradiol concentrations for the female fetuses may reflect early ovarian secretion.     

Gonadotrophins during second trimester of pregnancy: I. LH and hCG levels in maternal serum and amniotic fluid and their relationship to the sex of the foetus.

Luteinizing hormone and chorionic gonadotrophin levels were selectively measured by using radioimmunoassays in 98 maternal sera and 116 amniotic fluid samples obtained 10--20 weeks of pregnancy. Levels of hCG in serum were clearly high during 10--14 weeks and thereafter declined gradually. In contrast, serum concentrations of LH during 10--20 weeks were either unmeasurable (less than 1 ng/ml) or lower than those observed during the luteal phase of the menstrual cycle suggesting a decreased responsiveness of pituitary and/or a higher clearance rate for LH during this period of pregnancy. Neither LH nor hCG levels in maternal sera showed significant differences between male and female foetus bearers. A striking similarity was observed between maternal serum and amniotic fluid hCG patterns, despite hCG levels in maternal sera being always higher (1.5--26.9 fold). On the other hand amniotic fluid concentrations of LH became elevated following 12 weeks of gestation while maternal serum LH continued to be at low levels until 20 weeks. Furthermore a sexual dichotomy was observed in amniotic fluid LH concentrations but not in hCG levels during 14--20 weeks of pregnancy, with significantly lower LH levels in male foetus bearers than in female foetus bearers. Of interest is the clear demarcation in LH levels at 16 weeks of gestation. This sequential pattern of change in the concentrations of amniotic fluid LH is similar to those patterns reported by other investigators for foetal serum and pituitary LH during 10--20 weeks of gestation suggesting that the foetus may be the source of the increased levels of LH in amniotic fluid following 12 weeks of pregnancy.     

Foetal and maternal hormonal changes preceding normal bovine parturition

Successful chronic cannulation of the foetal posterior vena cava and maternal utero-ovarian and jugular veins in five Jersey cows between days 240 and 260 of gestation enabled changes in plasma hormone levels preceding calving to be monitored. All cows delivered live calves within the expected range of gestation for the breed. Corticosteroids were assayed by competitive protein-binding and prostaglandin F, progesterone, oestrone and oestradiol-17beta by radioimmunoassay. Foetal corticosteroids rose slowly from 5.0 +/- 0.7 ng/ml at 20 days to 9.3 +/- 3.0 ng/ml at 10 days before term, then progressively increased to a mean of 74 ng/ml, though higher concentrations occurred following surgery. Foetal oestrone and oestradiol-17beta concentrations were both less than 50 pg/ml and showed little change toward term. The maternal utero-ovarian oestrogens increased slowly from 20 to 10 days pre-partum and then rose more rapidly reaching peak levels (2.9 +/- 0.6 ng/ml for oestrone and 1.4 +/- 0.3 ng/ml for oestradiol-17beta) 1 to 4 days before delivery. Maternal progesterone concentrations fell towards term, with a rapid decrease over the last 36-48 h before calving when they gradually increased until the last 24 h where was a dramatic rise, reaching peak levels (5.7 +/- 0.6 ng/ml) during labour.     

Somatomedin in cord blood: relationship to gestational age and birth size.

Somatomedin (SM) was determined by bioassay in cord blood from 100 neonates born at 24-42 weeks of gestation and from three infants with major congenital malformations. SM levels rose with gestational age and had a positive correlation with birth weight, length and head circumference independantly of gestational age. These findings suggest a relationship between somatomedin and fetal growth.     

Gonadotrophins and ovarian steroids in cattle. II. Pulsatile changes of concentrations in the jugular vein throughout pregnancy

Short-term secretion patterns (derived from samples collected from jugular vein cannulae every 20 min for 12 h) of LH, FSH, progesterone, oestradiol-17 beta, oestrone and prolactin were studied every 30 days during gestation in heifers. LH pulse frequency and amplitude was greater during the early (months 1-3) and end (months 8-9) than during mid-gestation when pulsatile LH secretion was almost abolished. The frequency of pulsatile FSH release, which was already twice as fast than of LH during early pregnancy, did not change throughout the whole gestation period. Mean, basal and maximal progesterone concentrations were highest during the first 3 months of gestation, were slightly reduced during mid-gestation and decreased further during the last 2 months preceding parturition. Pulses of progesterone occurred concomitantly with the parallel LH/FSH as well as the separate FSH pulses. Average oestradiol-17 beta concentrations during the first months of gestation were slightly higher than during the mid-luteal phase of the cycle and exceeded during mid-gestation concentrations measured at oestrus. Free oestrone could be detected as early as day 60 of pregnancy. Frequency and amplitude of short-term changes of oestrone increased after the 5th month. Discontinuous secretion of oestrone as well as oestradiol-17 beta was only arbitrarily but never consistently correlated with either each other or with pulsatile gonadotrophin release. Apart form an occasional coincidence with pulsatile release of other hormones prolactin concentrations seemed to depend rather on the season of the year and time of the day than on the individual pregnancy stage.(ABSTRACT TRUNCATED AT 250 WORDS)     

LEVELS OF α-MELANOTROPHIN IN THE HUMAN FETAL PITUITARY GLAND THROUGHOUT GESTATION,IN ADULT PITUITARY GLAND AND IN HUMAN PLACENTA*

α-Melanotrophin was detected by radioimmunoassay in the human fetal pituitary gland from 11 weeks of gestation. The peak hormone concentration of 3.4 nmol/g pituitary tissue was reached at 17–20 weeks. From 17 to 36 weeks of gestation the total gland content rose gradually from 28 to 102 pmol. During this latter period, the pituitary gland grew some 10-fold, with the result that the α-melanotrophin concentration declined steadily to 1–3 nmol/g. In the final month of gestation, both the total gland content and the concentration of α-melanotrophin rose significantly to 254 pmol and 2.4 nmol/g respectively. The variations in pituitary gland content of α-melanotrophin were consistent with a role for pars intermedia peptides in the fetus. α-Melanotrophin-like peptides were not demonstrated in human placental tissue.     

Serum progesterone, estradiol-17 beta, and glucocorticoids in the collared peccary during gestation and lactation as influenced by dietary protein and energy

Sixteen pregnant collared peccaries were assigned to four experimental diets representing two levels of crude protein and two levels of digestible energy. Serum levels of progesterone, estradiol-17 beta (E2), and glucocorticoids were measured by radioimmunoassay. There was no significant dietary effect (P greater than 0.05) associated with any hormone during gestation. Progesterone did not differ between days 11 and 140 of gestation (X +/- SE = 36.48 +/- 1.11 ng/ml, N = 72), began to decline during the last week prepartum, and continued to decline within 24 hr of birth. Glucocorticoid concentrations remained level throughout gestation (X +/- SE = 6.57 +/- 0.45 microgram/dl, N = 74). E2 levels were low during the first 90 days of gestation, rose significantly (P less than 0.001) from 10.11 +/- 1.73 pg/ml (X +/- SE, N = 8) at Days 81-90 gestation to 49.07 +/- 12.87 pg/ml (N = 3) at 2-4 days prepartum (Days 141-147 of gestation), and declined rapidly to baseline levels within 24 hr of farrowing. Litter size had no effect on progesterone or E2 concentrations. There was no significant dietary effect on litter size or gestation length. During lactation, glucocorticoids and E2 remained stable and did not differ by diet, while progesterone concentrations appeared to be affected by diet. Individuals on the high energy-high protein diet returned to normal ovarian function before animals on the other three diets. Results indicated that the pregnant collared peccary can maintain a reproductive steroid environment that allows for fetal development in the face of moderate caloric or protein restriction and that the lactating peccary can undergo a postpartum ovulation in the presence of good nutrition.     

Identification of human luteinizing hormone, follicle-stimulating hormone, luteinizing hormone beta-subunit and gonadotrophin alpha-subunit in foetal and adult pituitary glands.

Specific radioimmunoassays were used to assess the content of LH, FSH, the gonadotrophin alpha-subunit and the LH beta-subunit in four adult, 19 normal foetal pituitary glands (9-5--32 weeks of gestation) and a pituitary extract from an anencephalic foetus (36 weeks). The hormones and subunits were further identified by column chromatography on Sephadex G-100. All pituitary glands contained free alpha-subunit and intact LH but the alpha-subunit:LH ratio was significantly higher in the early foetal pituitaries (9-5--16 weeks) than in the four adult pituitaries. Only small or undetectable amounts of LH beta-subunit and 'undetectable' FSH were found in these early foetal pituitaries (9-5--11-5 weeks). The concentration of intact hormones or subunits in the pituitaries showed no significant sex difference in any of the groups. In contrast to these results, only alpha-subunit was detectable in the pituitary of the anencephalic foetus. For 14 early foetuses (age of gestation 10--16 weeks) the serum levels of LH-HCG, FSH, and alpha-subunit in the circulation were significantly higher than in 26 foetuses at term (37--41 weeks). On the basis of these results a theory for the development of the gonadotrophin secretion from the foetal pituitary gland is outlined.     

Serum dehydroepiandrosterone sulfate in premature infants and infants with intrauterine growth retardation.

Serum dehydroepiandrosterone sulfate (DHAS) was measured by radioimmunoassay in blood samples obtained in 128 ill newborn infants. Serial sampling was carried out in 40 infants. There were wide ranges found in the values in all gestational age groups, and there were not significant differences in the first day of life between DHAS levels in less than 30 week gestation prematures, 6819 +/- 4631 (SD) ng/ml, and near term or term infants, 4307 +/- 1498 ng/ml. Mean DHAS concentrations did not decline over the first three weeks of life in prematures less than 36 weeks gestation. In six infants, age 35-73 days, and 29-34 weeks gestation at birth, the DHAS concentration was 1068 +/- 138 ng/ml. High concentrations were frequent in prematures less than 33 weeks gestation and could be correlated to epiodes of severe clinical stress. There were no significant differences in serum DHAS levels, on the first day of life, between infants with no hyaline membrane disease, nonfatal hyaline membrane disease and fatal hyaline membrane disease. Intrauterine growth retarded (IUGR) infants, who were greater than 35 weeks gestation, had significantly lower (P less than .032) DHAS levels in the first day of life than normally grown infants. The results show that there is a persistence during the postnatal period of the prominent delta5-3beta-hydroxysteroid production by the adrenal cortex characteristic of the fetus. Low concentrations of serum DHAS in IUGR infants suggest that the fetal zone of the neonatal adrenal cortex is a major source of circulating DHAS in the newborn period.     

Metabolic clearance rates (MCR) and production rates (PR) plasma progesterone in pregnant and pseudopregnant rabbits.

Our studies were designed to determine whether changing peripheral progesterone levels in rabbits reflected changing metabolic clearance rates (MCR) or changing production rates (PR), or both. Plasma progesterone concentrations rise from nonpregnancy levels to peak values at the end of the first third of gestation and at midpseudopregnancy. In the pregnant rabbit, these decline slowly during the second third of gestation and then more rapidly until near nonpregnancy values are reached at term. Progesterone levels decline sharply during the second half of pseudopregnancy. During pregnancy and pseudopregnancy, we found only small variations in MCRs which cannot account for the approximately 10-fold increase in plasma progesterone concentrations. The increases can, however, be accounted for by changes in PRs which rose sharply after conception of hCG injection to 14-fold the nonpregnancy level on day 16 of gestation and 11-fold on day 7 of pseudopregnancy. These results indicate that changes in ovarian PRs are the major factor for the variations in peripheral progesterone levels during pregnancy and pseudopregnancy. The rabbit differs in this respect from the guinea pig, in which changing progesterone concentrations during pregnancy were shown to reflect sharply reduced MCRs. After a single injection of progesterone in 20-day pregnant rabbits, the disappearance of the steroid from the circulation consisted of two components; an initial phase during which progesterone disappeared rapidly (t1/2 = 2.4 +/- 0.2 min) followed by a slower rate of disappearance (t1/2 = 21.5 +/- 2.2 min).     

Comparison of serum placental protein hormone levels in diabetic and normal pregnancy

Conflicting data exist concerning maternal serum concentrations of placental hormones during pregnancy in women with diabetes mellitus. To resolve some of these discrepancies, women participating in the NICHD-Diabetes in Early Pregnancy Study were studied. In this collaborative study, pregnancy was identified within 21 days of conception by serum hCG measurements. We prospectively collected 185 blood samples from 35 insulin-dependent diabetic women and 166 blood samples from 31 control women, all between 5 and 37 weeks gestation. Serum concentrations of hCG, pregnancy-specific beta-1-glycoprotein, placental lactogen, and hCG alpha were measured serially. The relationship between serum hormone, fasting blood glucose, 1-h postprandial blood glucose, and glycosylated hemoglobin concentrations was compared. Serum hCG alpha levels were significantly lower in the diabetic women than in control women at multiple time points during the first and second trimesters, while no consistent differences in the serum concentrations of hCG or pregnancy-specific beta-1-glycoprotein were found between pregnant diabetic and control women. Serum placental lactogen levels were significantly lower in diabetic women at 9-10 weeks and 20 weeks gestation. There were no correlations between fasting blood glucose, 1-h postprandial blood glucose, or glycosylated hemoglobin and any of the placental protein levels in the diabetic women. These data are consistent with a defect in synthesis and/or secretion of hCG alpha by the cytotrophoblast during the first two trimesters of pregnancy in insulin-requiring diabetic women.