Effect of maternal melatonin suppression during gestation on capuchin monkey (Cebus apella) fetal adrenal gland function

King's College London (2005) J Physiol 565P, C33

Communications: Effect of maternal melatonin suppression during gestation on capuchin monkey (Cebus apella) fetal adrenal gland function

Torres-Farfan, C ; Monso, C ; Valenzuela, F ; Viale, L ; Germain, A ; Campino, C ; Torrealba, F ; Valenzuela, G ; M, Seron-Ferre ;

1. Fisiologia, Pontificia Universidad Catolica de Chile, Santiago, Chile. 2. Obstetricia y Ginecologia , Pontificia Universidad Catolica de Chile, Santiago, Chile. 3. Endocrinologia, Pontificia Universidad Catolica de Chile, Santiago, Chile. 4. Women`s Health, Arrowhead , Regional Medical Center, Colton, CA, USA.

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Chronic maternal melatonin suppression by exposure to constant light in the last third of gestation, increases plasma cortisol concentration in the capuchin monkey early newborn (1). Melatonin inhibits ACTH-induced 3B-HSD expression and cortisol production by fetal adrenals in culture (1). To asses whether the increased cortisol in the newborn was due to effects on the fetal adrenal we studied the effects of chronic maternal melatonin suppression on: fetal adrenal weight and mRNA levels of 3B-HSD and the steroidogenic enzymes StAR, 11B-HSD1 and CYP21 and on in vitro steroid production (cortisol, progesterone and cortisone). Six pregnant female were maintained in constant light during the last third of gestation; 3 received a placebo (LL) and 3 received 500 ug/kg of melatonin daily (LL+Mel). 3 pregnant females in Light:Dark (14:10) were used as control. At 90% of gestation the females were sedated with ketamine (10 mg/kg) and anaesthetized with 1% halothane in oxygen. The fetuses were delivered by hysterotomy and immediately killed by an i.p. overdose of sodium thiopentone (100 mg/kg) (the remaining tissues from fetuses were frozen and stored at -80°C for later use). Fetal adrenals were dissected, weighed and cut in small explants (15 mg). Three explants were used to measure mRNA levels of 3B-SHD and steroidogenic enzymes (RT-PCR). The remaining explants were incubated 48-h in basal condition and plus 100 nM ACTH to measure steroids production in the supernatants (RIA). Approval was obtained from the local Ethics Committee. Results: Maternal melatonin supression (Table1) decreased fetal adrenal weight and increased 3B-HSD mRNA levels. Basal and stimulated, progesterone and cortisone production were increased, consistent with an increased 3B-HSD activity. These effects were reversed by maternal melatonin replacement. The treatments did not affect fetal weight, mRNA levels of steroidogenic enzymes or in vitro basal and stimulated cortisol production. Our results show a role of maternal melatonin in the regulation of the primate fetal adrenal gland. We speculate that maternal melatonin during gestation may have long term effects setting adrenal function for postnatal life.


Table1: Effects of maternal melatonin suppression (means &#177 SE) * vs other treatments p<0.05 ANOVA

Table1: Effects of maternal melatonin suppression (means &#177 SE) * vs other treatments p<0.05 ANOVA


Where applicable, experiments conform with Society ethical requirements.

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