Maternal Stress Decreases Steroid Aromatase Activity in Brains of Male and Female Rat Fetuses

Abstract

Steroid aromatase activity was measured in homogenates of combined hypothalamic and amygdaloid specimens obtained from 17- to 21-day-old male and female rat fetuses. The fetuses were obtained both from normal mothers and mothers exposed to a regimen of stress that results in a failure of behavioral masculinization and defeminization of male offspring. Tissue samples from stressed mothers and controls were obtained during the dark phase of the day (Villanova group, days 17, 18, 19, 20 and 21 postconception). Additional samples were obtained during the light phase (Hershey group, days 17.5, 18.5, 19.5 and 20.5 postconception). The aromatase assay used, based on the measurement of tritiated water formed during an incubation with [lβ-³H] androstenedione, had a sensitivity of 10–15 fmol per tube. There was no sex difference in aromatase activity in fetuses of either control or stressed mothers. When data from the two sexes were combined, the following sfatistically significant effects were identified: (1) lower aromatase activity in stressed compared with control fetuses on days 18, 19 and 20 postconception, (2) a progressive decline in enzyme activity between days 18.5 and 20.5 postconception in the Hershey group (controls) and between days 19 and 20 in both the control and stressed fetuses in the Villanova group, and (3) an increase in enzyme activity in the stressed fetuses between days 20 and 21. No relationship was evident between steroid aromatase activity in brain and circulating testosterone levels in male fetuses as determined in a previous study. Failure to detect sex differences or an effect of testosterone on aromatase activity could be due to tissue dilution since enzyme activity may be concentrated in a few discrete nuclear regions. Measurement of enzyme activity in these regions is needed before arriving at any definitive conclusions.

Effect of Sex, Intrauterine Position and Androgen Manipulation on the Development of Brain Aromatase Activity in Fetal Ferrets

“…In the fetal rhesus monkey no sex difference in aromatase activity was found in the POA or hypothalamus, and neither gonadectomy nor androgen treatment affected aromatase activity suggesting that this activity was not regulated by circulating androgens (13). Similarly, in the rat, Weisz et al (22) found no sex difference in aromatase activity of combined hypothalamic and amygdaloid tissues across Days E 17 to E21. However, George and Ojeda (23) reported a trend where aromatase activity in the POA of rats was higher in male than female fetuses on Day E22.…”

Hypothalamic Aromatase Activity in Male and Female Rats during Juvenile Peripubertal Development

“…The extracts were dried, reconsti tuted in 50 pi of chloroform, and applied to TLC plastic sheets pre-coated with silica gel (Brinkmann Instr. Inc., Westbury, N.Y.) that were developed in solvent systems and processed as previously outlined [2,22]. The isolated aeetylated steroids were processed and an aliquot was assayed for 5 H/ 14C radioactivity of the 3H product produced from the conversion of the substrate ([ 1,2,6.7-3H]T), which has a majority oflabel on the (t-positions ( > 65%), was compared to the recovery of the ra dioactive MC' standard to calculate the rate of hypothalamic aromatase activity.…”

“…The chloroform phase from the tritiated water assay incubations was used to determine 5a-reductase activity for each sample, as previously described [2,23], In brief, an aliquot o f the chloroform phase was dried down with 10 pg each of androslenedione; T; DHT; 5«-androstane-3u, 17|)-diol; 5a-androstane-3, 17-dione; 5(S-RHT; 5|S-androstane-3, 17-dione; 5(5-androstane-3a, 17|l-diol: and 5f)-androstane-3p, I7|i-diol. The steroids were resolved on TLC plastic sheets using dichloro- …”

“…Since 5a-reductase and aromatase activities decrease with puberty, a reduction in the ability of the hypothalamus to metabolize T to its active metabolites is expected. This may represent a factor determining the decreased sensitivity to steroid negative feedback that accompanies the completion of puberty.Brain aromatase activity is highest during prenatal develop ment in the rat [1][2][3]. The fact that estrogens can induce neural growth and arborization in the hypothalamus and amygdala [4][5][6], two sexually differentiated regions of the brain [7,8], sug gests that local formation of estrogens plays an integral role in the structural organization of these areas.…”

Asymmetry of Brain Aromatase Activity: Region- and Sex-Specific Developmental Patterns

“…Brain aromatase activity (AA) appers first in the diencephalon at gestational day (GD) 15 in male and female rat fetus [9], at about the time of onset and further development of estrogen receptors in hypothalamus and preoptic area (POA). Enzyme activity reaches its peak at around G D I9 in male and female rat fetuses to decline gradually with age [10,11]. Data on perinatal sexual dimorphism of this enzyme are controversial.…”