Endocrine Abstracts (2001) 2 P62

Sex differences in the pituitary-adrenocortical response to acute hypoxia in the ovine fetus during late gestation

DA Giussani, AJW Fletcher & DS Gardner


Department of Physiology, University of Cambridge, UK.


In the adult, females release more ACTH and adrenal steroids than males in response to stress, and these differences have been attributed to the stimulatory and inhibitory effects on the HPA axis of oestrogens and androgens, respectively (see Rivier, Pharm. Biochem. Behav. 64(4):739-751, 1999). The effects of sex differences on pituitary-adrenal responses to stress during fetal life remain unknown. This study compared the plasma ACTH and cortisol responses to acute hypoxia in male and female ovine fetuses during late gestation.

Seventeen male and 11 female fetuses were instrumented (halothane) with catheters at 125 days of gestation (term is ca. 145 days). At least 5 days after surgery, all fetuses were subjected to a 3 h protocol: 1 h normoxia, 1 h of hypoxia, and 1 h of recovery. Hypoxia was induced by reducing the maternal Fi,O2. Fetal arterial blood samples were taken during each experimental hour for measurement of blood gases and plasma concentrations of ACTH and cortisol (RIA). Basal plasma ACTH and cortisol were similar in male (38.5 ± 2.9 pg/ml, 23.4 ± 2.3 ng/ml) and female (32.3 ± 3.1 pg/ml, 22.2 ± 3.6 ng/ml) fetuses. During hypoxia, the falls in PaO2 (ca. 22 to 12 mmHg) and increases in plasma ACTH were similar in the two sexes (male: 387 ± 68; female: 416 ± 55 pg/ml. However the increase in plasma cortisol was significantly attenuated in female (39 ± 4 ng/ml) than in male (52 ± 5 ng/ml) fetuses (P<0.05). Correlation of paired plasma ACTH and cortisol concentrations showed that the slope of the linear relationship was higher in male (y = 0.08x + 22, R2 = 0.95) than female (y = 0.04x + 23, R2 = 0.90) fetuses (P<0.05).

These data suggest that adrenocortical sensitivity to acute stress differ between male and female ovine fetuses.

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