Somatomedin-like activity in plasma after foetal hypophysectomy or nephrectomy and in experimental intra-uterine growth retardation in sheep

Plasma samples from pregnant ewes and their foetuses during the last quarter of gestation were assayed for somatomedin-like activity (SLA) using the procine costal cartilage assay. In maternal plasma, the mean potency (compared with pooled serum from six sheep) was 0.84 +/- 0.05 (S.E.M.) units/ml (n = 15). Somatomedin-like activity in the plasma of five control foetuses (0.91 +/- 0.1 units/ml) was similar to the maternal levels and did not change with gestational age. After foetal hypophysectomy the SLA in foetal plasma (0.37 +/- 0.05 units/ml, n = 4) was significantly less than in control animals. In two nephrectomized foetuses, the mean SLA in plasma (0.08 and 0.51 units/ml respectively) was less than in control animals. Retardation of intra-uterine foetal growth was induced by removal of endometrial caruncles before pregnancy in four sheep. The SLA in plasma from these foetuses was 0.38 +/- 0.05 units/ml (P less than 0.01 v. control animals). The results suggest that SLA in the foetus may be important in the regulation of foetal growth, but they also indicate that factors other than growth hormone may be important in the control of SLA in foetal plasma.     

Maternal and foetal resistin and adiponectin concentrations in normal and complicated pregnancies

OBJECTIVE: The aim of this study was to evaluate how resistin and adiponectin (ApN) are involved in maternal energy metabolism and foetal growth. DESIGN: A cross-sectional study. PATIENTS AND MEASUREMENTS: Resistin and ApN were measured in 30 healthy nonpregnant women, 73 pregnant women [10-41 weeks of gestation; 18 with gestational diabetes mellitus (GDM), five with pregnancy-induce hypertension (PIH), nine with pre-eclampsia (PE), eight with chronic hypertension (CH) and 33 normal] and 40 foetal samples (20-41 weeks of gestation; 18 from GDM mothers and 22 from normal mothers). RESULTS: Resistin levels were significantly higher in normal pregnant women than in nonpregnant controls (13.7 +/- 2.1 vs. 6.3 +/- 1.6 ng/ml; P < 0.005) and showed a negative correlation with gestational age (P < 0.0001, r = -0.7). Only women with PE presented resistin levels significantly lower than normotensive women of the same gestational age (8.2 +/- 1.2 vs. 17.9 +/- 4.3 ng/ml; P < 0.005). ApN levels, although similar in normal pregnant women to those in nonpregnant controls, were significantly lower in women with GDM (37-41 weeks; 5.2 +/- 0.5 vs. 8.2 +/- 0.8 mg/l; P < 0.0001) and PE (20-37 weeks; 5.0 +/- 0.7 vs. 9.5 +/- 0.7 mg/l; P = 0.008) than those found in normal women matched for gestational age. Resistin was detected in the umbilical venous blood in foetuses from 20 to 41 weeks of gestation. In all newborns, both resistin and ApN levels were significantly higher than those recorded in adult life and did not correlate with maternal levels (P = ns, r = 0.03 for resistin and P = ns, r = -0.3 for ApN). Foetuses from diabetic mothers had ApN significantly lower than normal foetuses (26.8 +/- 2.6 vs. 37.5 +/- 3.5 mg/l; P = 0.02), while resistin levels were similar (17.3 +/- 3.7 vs. 18.2 +/- 1.5 ng/ml; P = ns). CONCLUSION: The secretion pattern of ApN in normal and complicated pregnancies strongly suggests an involvement of ApN in insulin resistance during gestation, while resistin seems to have a minor role. Moreover, the detection of high levels of resistin and ApN in cord blood during gestation is consistent with a regulatory action of these adipokines on tissue differentiation and foetal growth.     

The ontogeny and regulation of corticosteroid secretion by the ovine foetal adrenal.

Adrenal glands of foetal sheep of 40 days gestation to term were incubated with and without ACTH or an increased [K-+]. With ACTH, the 40 day foetal adrenal was capable of producing more cortisol and aldosterone per g body weight than was the term adrenal. ACTH was a potent stimulus to aldosterone and cortisol production in foetuses aged 60-90 days, and this effect declined significantly in the 91-120 day period. An increased [K-+] was stimulatory to aldosterone production only after 120 days gestation. Peripheral blood levels of aldosterone, corticosterone, cortisol, 11-deoxycortisol and 11-deoxycorticosterone were measured in foetuses 60 days to term and the levels of aldosterone and cortisol were significantly lower in 90-120 day foetuses than in the younger or older ones. Direct adrenal vein cannulation proved all five steroids to be secretory products of the foetal adrenal.     

NSILA and foetal growth.

Employing a sensitive competitive protein binding assay for NSILA (non-suppressible insulin-like activity), circulating levels of this somatomedin (SM) have been measured throughout pregnancy, at parturition, and in foetal and newborn sera. Acid-dissociable serum NSILA (mean +/- SEM) in 57 women was significantly higher during pregnancy (1106 +/- 46 microunits/ml), than in 11 adult non-pregnant control subjects (844 +/- 22 microunits/ml), but not correlated with week of gestation or with serum growth hormone (GH) or cortisol levels. At parturition, the NSILA concentration in 28 cord sera (598 +/- 38 microunits/ml) was significantly less than in the corresponding maternal sera (1039 +/- 63 microunits/ml). The NSILA levels in 23 premature newborns (370 +/- 20 microunits/ml) and 8 small-for-gestational-age newborns (310 +/- 46 microunits/ml) were significantly less than in 33 term newborns (494 +/- 18 microunits/ml). Serum NSILA in 56 term and premature newborns exhibited a significant positive correlation both with gestational age and birth weight but not with serum GH or cortisol levels. These data suggest that the maternal-foetal growth-promoting system is a highly complex one in which NSILA levels both in maternal and foetal circulations appear to be under multifactorial control.     

Changes in the concentration of adrenocorticotrophin and corticosteroid in the plasma of foetal sheep in the latter half of pregnancy and during labour.

The changes in plasma ACTH concentration of pregnant sheep and their foetuses during the latter half of pregnancy and during labour were studied. Before 140 days of gestation the mean concentration in foetal arterial plasma was 117+/-19 (S.E.M.) pg/ml which rose to a mean of 286+/-63 pg/ml. The rise in ACTH occurred at about the same time as, but not before, the rise in corticosteroid concentration in foetal plasma. The maternal plasma ACTH concentration did not change during the latter half of pregnancy and had a mean concentration of 64+/-9 pg/ml. During labour there was a progressive rise in the ACTH concentration in foetal plasma which was not associated with any corticosteroid changes. Ethanol did not suppress labour but reduced the ACTH concentration in foetal plasma.     

Progesterone 20 alpha-dihydroprogesterone and 20 beta-dihydroprogesterone levels in different compartments from the human foeto-placental unit.

The endogenous levels of progesterone, 20 alpha-dihydroprogesterone and 20 beta-dihydroprogesterone in different foetal tissues, in placental tissue and in foetal blood during pregnancy (week 9-25) were determined by gas-liquid chromatography or by radioimmunoassay. The identification of these steroids in foetal tissues was based on the behaviour in paper and thin-layer chromatography, the formation of different derivatives, and the retention times in gas-liquid chromatography. For additional identification of progesterone and 20 alpha-dihydroprogesterone a mass spectrum was obtained. The average concentrations of progesterone (P), 20 alpha-dihydroprogesterone (20 alpha-DHP) and 20 beta-dihydroprogesterone (20 beta-DHP) in foetal tissues were as follows (ng/g wet weight tissue): brain, P 119.0 +/- 45.5, 20 alpha-DHP 86.9 +/- 44.7 and 20 beta-DHP 9.7; lungs, P 257.7 +/- 195.7, 20 alpha-DHP 60.3 +/- 26.4 and 20 beta-DHP 7.8; liver, P 103.7 +/- 84.6, 20 alpha-DHP 95.2 +/- 89.8 and 20 beta-DHP 17.8; adrenals, P 295.7 +/- 90.0 20 alpha-DHP 254.5 +/- 194.6; kidneys, P 214.2 +/- 155.3 and 20 alpha-DHP 76.6 +/- 43.0; intestine, P 273.2 +/- 166.7, 20 alpha-DHP 77.9 +/- 51.2 and 20 beta-DHP 8.7; residual tissues, P 246.3 +/- 178.3 and 20 alpha-DHP 54.8 +/- 44.5. The average concentrations in placental tissue and in foetal plasma (week 12-18) were as follows (ng/g wet weight tissue or ng/ml plasma): placenta, P 2619. +/- 2153.6 and 20 alpha-DHP 461.0 +/- 155.9; foetal plasma, P 378.7 +/- 231.8 and 20 alpha-DHP 283.0 +/- 108.9. These results indicate that some foetal organs contain a high 20 alpha-reductase activity at least during the first half of pregnancy.     

Evidence that cortisol inhibits basal adrenocorticotropin secretion in the sheep fetus by 0.70 gestation

To ascertain if reductions in fetal plasma cortisol cause increases in fetal plasma ACTH, we treated pregnant ewes or their fetuses with aminoglutethimide (10 mg/kg BW) and metyrapone (20 mg/kg BW) and measured the hormonal responses with RIAs. When given to fetuses (n = 9) at 0.90 +/- 0.01 gestation (term-145 days), the steroid synthesis inhibitors reduced fetal plasma cortisol from 35.1 +/- 11.9 to 18.5 +/- 6.2 ng/ml (P less than 0.01) and plasma ACTH increased from 37 +/- 7 to 189 +/- 74 pg/ml (P less than 0.02). Thus, late in gestation cortisol from the fetal adrenal suppresses basal fetal ACTH secretion. Blockade of steroid biosynthesis in pregnant ewes carrying intact fetuses at 0.76 +/- 0.02 gestation (n = 11) or adrenalectomized fetuses at 0.81 +/- 0.01 gestation (n = 6) also reduced cortisol and increased ACTH in fetal plasma. In intact fetuses cortisol declined from 9.4 +/- 2.0 to 3.6 +/- 0.9 ng/ml (P less than 0.05), and ACTH increased from 46 +/- 8 to 183 +/- 67 (P less than 0.01); cortisol declined in adrenalectomized fetuses from 2.1 +/- 0.4 to 1.1 +/- 0.3 ng/ml (P less than 0.01), and ACTH increased from 106 +/- 13 to 400 +/- 104 pg/ml (P less than 0.01). Cortisol infusions into intact and adrenalectomized fetuses prevented both the decline in steroid concentration caused by the biosynthesis inhibitors given to the ewe and the increase in fetal plasma ACTH concentration. These data indicate that reductions in plasma cortisol in adrenalectomized fetuses or intact fetuses at a time in development when the fetal adrenal produces little cortisol cause compensatory increases in fetal plasma ACTH concentration. The simplest explanation for these observations is that from approximately 0.70 gestation, basal fetal ACTH secretion is tonically inhibited by cortisol circulating in fetal plasma. This cortisol can originate from sources other than the fetal adrenal.     

The effect of maternal thyroidectomy prior to conception on foetal brain development in sheep

Merino ewes were surgically thyroidectomized, and mated 6 weeks later when their plasma thyroxine (T4) levels were negligible. Their foetuses were delivered by hysterotomy at 52, 71, 84, 98, 125, 140 days gestation or at term (150 days). Despite the very low levels of T4 in maternal plasma, the concentrations of T4 in foetal plasma were not significantly different after 71 days gestation from those of foetuses of sham-operated (control) ewes. Foetal brain and body weights, however, were reduced from 71 days compared to those of foetuses of sham-operated ewes. The foetal brain weights but not the body weights were restored to normal from 125 days to term. In addition to the weights, cell number (DNA) and cell size (protein:DNA ratio) appeared to be normal in the neonatal brain at parturition and this was confirmed by histological examination of the brains. Thus lack of maternal thyroid hormones in early pregnancy may cause a reduction in brain and body growth in the foetus which, in the case of the brain, appears to be restored to normal after the onset of foetal thyroid function.     

Studies on insulin-like growth factors (IGF-I, -II) and there binding proteins in normal human pregnancy

In order to elucidate the roles of Insulin-like Growth Factors (IGF-I, -II) in human pregnancy, the levels of IGF-I and IGF-II, the distribution of binding proteins for IGF-I or IGF-II and profiles of unsaturated somatomedin binding proteins (USBP) were estimated in maternal and cord plasma. IGF-I levels in maternal plasma gradually elevated in late gestation, reaching 304.4 +/- 130.1ng/ml at term, and were significantly higher than those in nonpregnant women (188 +/- 58). IGF-II levels, which were 414.9 +/- 75.4ng/ml in women in the third trimester of gestation, did not produce any remarkable changes in the levels in nonpregnant women (395.9 +/- 72.6). On the other hand, IGF-I in cord plasma also increased according to gestational age, reaching 37.3 +/- 14.6ng/ml at term, but it was significantly lower than that in maternal weight (r = 0.50, p less than 0.005) and relative birth weight (r = 0.41, p less than 0.005). IGF-II in cord plasma showed no significant changes during gestation, however, IGF-II levels in AFD (appropriate for date) newborns delivered at term (203.8 +/- 59.4) were significantly lower than those in maternal plasma. And they had no positive correlations with birth weight and relative birth weight. On Sephadex G150 gel-chromatography of cord plasma from AFD newborns at term, more than 70% of immunoreactive IGF-I in plasma was eluted at 150K region, and 150K USBP could be detected as observed in adult plasma. On the other hand, most of the immunoreactive IGF-II was eluted at 40K region, and 150K USBP was not detected in AFD newborns at term. In adult plasma, most of the immunoreactive IGF-II was eluted at 150K region, but 150K USBP could not be detected. From these results, it is supposed that IGF-I plays an essential role in fetal growth rather than IGF-II.     

Circulating forms of human foetal somatomedin

Two forms of somatomedin, which crossreact in a radioreceptor-assay using foetal brain membranes as matrix, have been partially purified from the serum of human foetuses aged 16-28 weeks of gestation. The purification scheme consisted of acid precipitation, Sephadex G-50 chromatography, affinity chromatography and cation exchange fast protein liquid chromatography. The two peaks of activity had apparent molecular weights of approximately 7000 and different isoelectric points. The elution positions of these peaks corresponded to the elution positions of the truncated IGF-1 variant and intact IGF-2, respectively.     

Studies of oxytocin in the baboon during pregnancy and delivery.

Oxytocin was determined by radioimmunoassay in pregnant baboons throughout gestation, in the foetus at caesarean section, and after oxytocin infusion into the mother and foetus. Serial maternal plasma oxytocin in 6 baboons during pregnancy showed a significant correlation between the gestational age and maternal plasma oxytocin concentrations with a correlation coefficient of r = 0.3185 and P less than 0.005. Seventy-one out of 75 plasma samples (94.7%) during pregnancy had detectable levels of oxytocin. Uterine vein plasma had higher oxytocin concentrations than maternal plasma and amniotic fluid (18.6 +/- 4.6 pg/ml; mean +/0 SE) but lower than umbilical, jugular vein and cardiac blood from the foetus. Foetal pituitary gland contained 5.4--26.1 micrograms oxytocin/g. Regular uterine contractions were established with iv oxytocin of 4--20 mU/min and the plasma oxytocin measured showed a significant correlation with the uterine activity achieved (r = 0.64, P less than 0.001). The disappearance of plasma oxytocin at 179 days gestation gave an apparent half-life of 1.1 and 1.7 min in 2 baboons with a late half-life of 9.9 and 17.3 min, respectively. In one baboon at 171 days gestation, the apparent half-life of oxytocin was 9.9 min. The metabolic clearance rates were calculated to be 3.1, 3.2 and 11.7 ml/kg/min, respectively. The production rates were 97, 74, 390 pg/kg/min, respectively. Oxytocin injected into the umbilical vessel near term showed an increase in oxytocin concentration in maternal and uterine vein plasma and amniotic fluid, suggesting that oxytocin can cross the placenta from the foetal to the maternal side. Our findings indicate that in the baboon (1) oxytocin is present throughout pregnancy, (2) uterine activity can be correlated with plasma oxytocin during oxytocin infusion, (3) foetal circulation has higher oxytocin concentration than maternal blood and (4) oxytocin probably can cross the placenta from the foetus to the mother.     

Genetic selection for insulin-like growth factor-1 in growing mice is associated with altered growth

Substantial responses in the 6-week and mature body-weights of mice occurred after 7 generations of selection for or against plasma levels of Insulin-like Growth Factor-1 (IGF-1). Plasma levels of IGF-1 were also significantly different after 7 generations of selection (high line = 85 +/- 2 ng/ml, low line = 58 +/- 2 ng/ml). The average 6-week weight in the line selected for high plasma IGF-1 was 22.5 +/- .2 g compared with 18.5 +/- .2 g in the low plasma IGF-1 line, after 7 generations of selection. The difference between lines was maintained at 20 weeks of age. These data provide further evidence for the roles of IGF-1 in the regulation of somatic growth and as a mediator of a genetic component of growth.     

Protein binding of plasma cortisol in the foetal lamb near term.

Binding of cortisol to plasma proteins was studied in the foetal lamb by equilibrium dialysis at 37 degrees C. At 122 days of pregnancy the mean level of transcortin expressed as cortisol-binding capacity was 28 +/- 6 (S.D.) ng cortisol/ml plasma. During the last 14 days of pregnancy there was a progressive increase in transcortin-binding capacity to 85 +/- 14 ng cortisol/ml plasma. A sharp increase in the concentration of both protein-bound and unbound cortisol was observed over the same period. A rise in the concentration of total cortisol from around 3 to 42 ng/ml was associated with an increase in unbound cortisol from 0-2 to a maximum of 2-1 ng/ml. The concentration of albumin-bound cortisol was approximately equal to that of unbound cortisol. The mean value for the transcortin-cortisol affinity constant was 1-15 x 10(8) l/mol. It is concluded that an increase in transcortin-binding capacity is partly responsible for the prepartum increase of corticosteroid levels observed in normal foetal lambs.     

Prolactin responses, menstrual cycles, and body composition of women runners

Fourteen young women with normal menses participated in an endurance running program to investigate the effects of physical training on menstrual function, plasma PRL, and body composition. Body composition, measured by hydrostatic weighing, and PRL (basal and TRH-stimulated ) were determined initially and after each subject had increased her weekly mileage by 30 miles (delta 30) and 50 miles (delta 50). Mean (+/- SEM) total body weight did not change, but the subjects became significantly leaner (relative fat, 25.5 +/- 1.3% at baseline vs. 22.4 +/- 0.9% at delta 50; P less than 0.02). Thirteen women developed menstrual changes (mainly oligomenorrhea), but not amenorrhea. Mean (+/- SEM) unstimulated PRL levels were 16.8 +/- 3.1%, 16.9 +/- 2.4, and 11.5 +/- 2.1 ng/ml at baseline, delta 30, and delta 50, respectively (P less than 0.03 at delta 50 compared to baseline and delta 30). Mean ( +/- SEM) integrated TRH-stimulated PRL responses increased from 5002 +/- 462 ng/ml.min at baseline to 5748 +/- 609 mg/ml.min at delta 30 and 6535 +/- 552 ng/ml.min at delta 50, and were significantly different from one another (F = 4.01; P less than 0.04). Endurance training, without total body weight loss or extreme leanness, results in frequent menstrual dysfunction. Other authors have shown that young female athletes have an increased PRL response to acute exercise compared to nonathletes. One mechanism responsible for menstrual dysfunction in endurance-trained women may be frequent and exaggerated PRL responses to exercise and other stimuli.     

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.     

Maternal and foetal corticosterone levels during late pregnancy in rats.

Adrenal and plasma corticosterone levels were determined in rat foetuses and in intact or adrenalectomized mothers during late pregnancy. Foetal adrenal and plasma corticosterone concentrations reached a peak on day 19 of pregnancy, while maternal plasma corticosterone increased on day 18 and remained high until parturition. From day 18, mothers adrenalectomized on day 14 had corticosterone levels similar to those of intact pregnant rats. At every stage of gestation (except day 21) plasma corticosterone levels were higher in the foetuses than in the mothers. The corticosterone concentration in the maternal plasma correlated with the number of live foetuses during the last 3 days of gestation. These results suggest that corticosterone can cross the placenta from foetus to mother as early as day 18 and that the foetus contributes to the maternal corticosterone pool after day 18.     

Altered growth hormone and prolactin responses to dopaminergic stimulation in Huntington's chorea.

Seven patients affected by Huntington's chorea were given an acute administration of 2-Br-alpha-ergocryptine (CB 154, Sandoz), a direct agonist at dopamine receptor sites. Seven nonobese hospitalized patients were used as controls. Oral administration of CB 154 (2.5 mg) induced a more prompt and consistent rise in plasma growth hormone (GH) levels in patients than in controls. GH levels rose from baseline values of 0.3+/-0.1 ng/ml to mean peak values of 20.4+/-5.1 ng/ml (120-270 min) in choreic subjects and from baseline values of 1.0+/-0.4 ng/ml to mean peak values of 5.7+/-1.6 ng/ml (180-300 min) in control subjects (P less than 0.02). Baseline plasma prolactin (PRL) values were significantly higher in choreic than in control subjects (22.1+/-6.6 ng/ml vs. 8.1+/-1.4 ng/ml, respectively, P less than 0.02); administration of CB 154 induced a more consistent PRL decrease in control than in choreic subjects. Collectively, these results suggest the existence of an abnormal regulation of GH and PRL secretion in Huntington's chorea, probably due to alterations in central dopaminergic neurotransmission.     

The hypothalamic-pituitary-testicular axis in thyrotoxicosis.

The hypothalamic-pituitary-testicular axis was evaluated in seven men with thyrotoxicosis due to Graves' disease. Loss of libido and decreased potency were present in 71% and 56%, respectively. All patients had normal testicular volume (25 ml in all) and gynecomastia was detected in two of seven patients. Total sperm counts were less than 40 million in four of the five men tested. There was an inverse correlation between basal serum 17 beta-estradiol (E2) levels and total sperm count (r = -0.87; P less than 0.05). Mean (+/- SE) total testosterone (T) and E2 levels (1008 +/- 104 ng/100 ml and 104 +/- 16 pg/ml) were significantly higher than in normal men (P less than 0.05). Free T (13.6 +/- 2.4 ng/100 ml) was indistinguishable from normal (15.3 +/- 1.5 ng/100 ml). The mean (+/- SE) response of serum T to hCG administration was blunted (80 +/- 40%) compared to controls (193 +/- 19%; P less than 0.02). Basal plasma LH levels (15.5 +/- 1.5 mIU/ml) were significantly higher (P less than 0.05) than in normal men (9.1 +/- 0.6 mIU/ml) and hyperresponded to 100 microgram LRH iv in five of seven patients. Basal plasma FSH levels and the FSH response to LRH were normal. These results suggest that men with hyperthyroidism have 1) partial Leydig cell failure, 2) impairment of spermatogenesis, and 3) blunting of the feedback effects of E2.     

Estrogen stimulates growth hormone and somatomedin-C in castrate and intact female baboons

To evaluate the effects of physiological concentrations of estrogen on plasma concentrations of somatomedin-C (Sm-C) and GH, 16 chronic castrate female baboons were implanted either with blank Silastic capsules (n = 5) or capsules containing crystalline estradiol (E2; n = 11), which remained in place for 7 days. By day 7, serum E2 levels in treated animals rose into the physiological adult female range (mean +/- SEM, 96 +/- 9.2 pg/ml) and were greater (P less than 0.0005) than those in control animals (27.5 +/- 3.4 pg/ml). Sm-C concentrations rose significantly by day 7 in treated animals compared to those in control animals, whether assayed from unprocessed plasma (96% increase; P less than 0.01), plasma pretreated with glycine-HCl (99% increase; P less than 0.01), or plasma extracted with acid-ethanol (72% increase; P less than 0.02). GH concentrations in these animals were low and were not significantly different in E2-treated and control animals. To evaluate the effects of pharmacological doses of E2 on Sm-C and GH concentrations, six intact adult female baboons were treated with six daily injections of 1 mg E2 benzoate in oil. Serum E2 rose to a mean level of 1669 +/- 320 pg/ml on day 7. The plasma Sm-C concentration by day 7 was significantly higher than the pretreatment value whether assayed in untreated plasma (4.3-fold increase; P less than 0.01), plasma pretreated with glycine-HCl (2-fold increase; P less than 0.01), or plasma extracted with acid-ethanol (1.7-fold increase; P less than 0.01). Mean serum GH concentrations rose significantly from 3.3 ng/ml on day 0 to 23.6 ng/ml by day 7 (P less than 0.02). Evaluation of the chromatographic profile of native baboon plasma suggested a marked increase in [125I]Sm-C binding to plasma proteins after in vivo pharmacological E2 treatment; a broad peak of [125I]Sm-C binding over a size range from that of albumin to gamma-globulin was found. These results indicate that estrogen treatment of castrate or intact female baboons with both physiological and pharmacological doses results in an increase in plasma Sm-C concentrations that, at least in pharmacological doses, are mediated through an increase in GH concentrations. Although pharmacological E2 treatment results in a stimulation of plasma proteins that bind Sm-C, the effects on plasma Sm-C concentrations were found after procedures that diminish interference from circulating binding proteins. These data support the concept that estrogen may play a role in the physiological increase in plasma concentrations of Sm-C associated with normal puberty.     

Relationship between plasma somatomedin-C and liver somatogenic binding sites in neonatal rats during malnutrition and after short and long term refeeding

To determine the mechanism(s) for the growth retardation associated with malnutrition early in life, the relationships among plasma somatomedin-C (SM-C), plasma GH, and hepatic bovine GH-binding sites were assessed in rat pups that were milk-deprived from birth until weaning (21 days). After this period of malnutrition, body weight, tail length, plasma SM-C, and liver GH-binding capacity of the malnourished animals were significantly (P less than 0.001) reduced below those of control, well fed rats [SM-C at 21 days, 0.06 +/- 0.01 vs. 0.30 +/- 0.04 U/ml (mean +/- SE); GH binding, 2.96 +/- 0.39 vs. 7.19 +/- 0.80 pmol/liver]. The number of GH-binding sites per mg DNA was also reduced (0.59 +/- 0.06 vs. 1.08 +/- 0.11 pmol/mg DNA; P less than 0.001). After 1 week of ad libitum refeeding (days 21-28), body weight and tail length of malnourished pups increased significantly but showed no signs of catching up with that of control pups. Plasma SM-C and liver GH-binding capacity in the malnourished rats also rose significantly (P less than 0.005) after refeeding, but remained as far below controls as at 21 days [SM-C on day 28, 0.19 +/- 0.02 vs. 0.53 +/- 0.02 U/ml (P less than 0.001); GH binding, 6.59 +/- 0.99 vs. 12.94 +/- 1.60 pmol/liver (P less than 0.005)]. After 7 weeks of refeeding (days 21-70), tail length but not body weight recovered, while plasma SM-C levels were normalized. The mean number of GH binding sites per mg DNA in the malnourished rats was not significantly different from that in controls and reached for the males and the females, respectively, 79% and 86% of control binding. When expressed per liver, GH binding followed a similar pattern; for the males, binding capacity returned to 73% of the control value (20.45 +/- 1.82 vs. 27.93 +/- 3.49 pmol/liver; P = NS), and for the females, it returned to 77% of the control value (36.42 +/- 1.76 vs. 47.42 +/- 4.13 pmol/liver; P less than 0.01). In the young rats up to day 28, liver GH-binding capacities correlated with plasma SM-C concentrations (r = 0.81; P less than 0.01), while in the adult rats no correlation was present. During malnutrition and refeeding, there were no changes in the affinity constants of the hepatic GH-binding sites or in plasma GH concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)