The effects of burn trauma in men on the production of adrenal and testicular steroids was investigated. Whereas there were significant increases in serum cortisol levels and urinary 17-hydroxycorticosteroid excretion soon after thermal injury, there were significant decreases in serum dehydroepiandrosterone sulfate, dehydroepiandrosterone, androstenedione, and testosterone concentrations during the first 4 weeks following burn trauma. Serum androstenediol and androstenediol sulfate levels also were reduced, though insignificantly, 10-23 days postburn. Serum LH levels were unchanged during the postburn interval. Since urinary 17-ketosteroid excretion was normal or below normal rather than increased, the decline in serum C19-steroid levels probably resulted from decreased glandular secretion rather than increased rates of metabolism and excretion. Low dehydroepiandrosterone sulfate and/or testosterone levels were found in some men several months after recovery from their burns. These data suggest that thermal injury leads to acute inhibition of adrenal and testicular C19-steroid secretion, but stimulation of adrenal glucocorticosteroid production, and that endocrine function in many instances is not normalized after complete healing of the burned surfaces. The mechanisms and physiological consequences of such changes in the steroid milieu of men after burn trauma are unknown.

The mechanisms that lead to the steroidogenic differences in the human fetal adrenal (HFA) and adult adrenal gland are not known. However, gene expression clearly plays a critical role in defining their distinct steroidogenic and structural phenotypes. We used DNA microarrays to compare expression levels of several thousand transcripts between the HFA and adult adrenal gland. Total RNA was isolated from 18 HFA and 12 adult adrenal glands. Samples of total RNA were used to make five pools of poly A+ RNA (mRNA). Gene profiling was done using five independent microarrays that contained between 7075 and 9182 cDNA elements. Sixty-nine transcripts were found to have a greater than 2·5-fold difference in expression between HFA and adult adrenals. The largest differences were observed for transcripts that encode IGF-II (25-fold higher in HFA) and 3 -hydroxysteroid dehydrogenase (24-fold higher in adult). Among the other genes, transcripts related to sterol biosynthesis or to growth and development were higher in the HFA than adult adrenals. Transcripts concerned with cellular immunity and signal transduction were preferentially expressed in the adult adrenal. The vast majority of the 69 transcripts have not been studied with regard to adrenal function. Thus, these gene profiles provide valuable information that could help define the mechanisms that control adrenal function.

No abstract

No abstract

ABSTRAm. The results of prior studies suggest that abnormalities of development and function of the fetal adrenal occur in pregnancies complicated by intrauterine fetal growth retardation (IUGR). In the present investigation, we sought to extend such studies by matching IUGR infants with normally grown infants of women in whom pregnancy complications, delivery method, and gestational age were comparable. In 47 vaginally delivered, IUGR infants (38 f 2 wk, mean f SD; 2244 f 589 g body weight), the levels of dehydroepiandrosterone sulfate (DS) in umbilical cord serum (4.48 f 2.94 pmol/L) were lower ( p = 0.035) than those (5.94 f 3.63 pmol/L) of 47 normal weight infants (38 f 2 wk; 3107 f 527 g). Yet, umbilical cord serum levels of cortisol in IUGR infants (455 f 189 nmol/L) were slightly higher than those of the control infants (408 f 247 nmol/L). The DS/cortisol molar ratio in IUGR infants (10.5 2 6.8) was 41% lower ( p = 0.0013) than that of the control infants (17.7 f 13). Also, the estimated DS plasma pool in IUGR infants (521 f 349 nmol) was strikingly lower ( p = 0.0018) than that of the control infants (800 f 480 nmol); the estimated plasma pools of cortisol were equivalent (growth-retarded: 53 f 27 nmol; control: 55 f 34 nmol). Although we anticipated that total cholesterol and apo B levels in IUGR infants would be increased due to reduced adrenal utilization of LDL for DS production, such was not the case. We conclude that a selective deficiency of DS production occurs in the IUGR fetus. (Pediatr Res 35: 633-636, 1994) Abbreviations IUGR, intrauterine growth retardation or retarded DS, dehydroepiandrosterone sulfate PIH, pregnancy-induced hypertension Estrogen production in human pregnancy is largely dependent on the production of DS by the fetal adrenals and subsequent aromatization of DS and 16 hydroxy-DS (formed in the fetal liver from DS) in the placenta. In normal fetuses, plasma DS concentrations seem to remain relatively constant during the latter half of gestation with the exception of a progressive rise during the last 6-8 wk of intrauterine life (I). Thus, the fetal plasma pool of DS increases steadily between approximately 20 and 32 wk in concert with fetal growth and then increases strikingly near term (I), giving rise to the accelerated increase in estrogen production that occurs at this time (2,3). In pregnancies complicated by IUGR, maternal estrogen levels are usually sub- normal (4, 5). Impaired estrogen production in such circumstances could result from several factors, including reduced mass of the placenta wherein estrogen formation occurs and decreased adrenal production of DS by the growth-retarded fetus. We (3,6-8) and others (9) have found subnormal DS concentrations in umbilical cord blood of infants believed to be stressed in utero as a consequence of various pregnancy complications. On the other hand, many such infants have normal to increased cortisol levels (6-8). Such findings are suggestive of stress-associated alterations in the adrenal steroid biosynthetic pathway. The...