Prenatal Ethanol Exposure Alters the Effects of Gonadectomy on Hypothalamic‐Pituitary‐Adrenal Activity in Male Rats

Abstract

Prenatal ethanol exposure has marked effects on development of the hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes. In adulthood, ethanol-treated rats show altered gonadal hormone responses and reproductive function, and increased HPA responsiveness to stressors. Importantly, prenatal ethanol differentially alters stress responsiveness in adult males and females, raising the possibility that the gonadal hormones play a role in mediating prenatal ethanol effects on HPA function. To examine a possible testicular influence on HPA activity in males, we compared the effects of gonadectomy on HPA stress responses of adult male offspring from ethanol, pair-fed (PF) and ad libitum-fed control dams. Intact ethanol-treated rats showed increased adrenocorticotrophic hormone (ACTH) but blunted testosterone and luteinising hormone (LH) responses to restraint stress, and no stress-induced elevation in arginine vasopressin (AVP) mRNA levels compared to those observed in PF and/or control rats. Gonadectomy: (i) significantly increased ACTH responses to stress in control but not ethanol-treated and PF males; (ii) eliminated differences among groups in plasma ACTH and AVP mRNA levels; and (iii) altered LH and gonadotrophin-releasing hormone responses in ethanol-treated males. Taken together, these findings suggest that central regulation of both the HPA and HPG axes are altered by prenatal ethanol exposure, with normal testicular influences on HPA function markedly reduced in ethanol-treated animals. A decreased sensitivity to inhibitory effects of androgens could contribute to the HPA hyperresponsiveness typically observed in ethanol-treated males.

Prenatal alcohol exposure and prenatal stress differentially alter glucocorticoid signaling in the placenta and fetal brain

“…It is possible that the lower estradiol, and hence the higher progesterone/estradiol ratio seen in PAE compared to dams in the other treatment groups may contribute to the delayed parturition that often occurs with prenatal alcohol exposure. Indeed, we (Lan et al, 2006; Weinberg 1985) and others (Bond 1982) have shown that alcohol intake delays parturition in animal models of PAE and in the past, alcohol drip has been used clinically to stop premature labor (Fuchs et al, 1967). Furthermore, in the rat, the first half of pregnancy is established and maintained by hormones released from the anterior pituitary and ovaries, but the placental hormones are the driving factors during the second half of pregnancy (Taya and Greenwald, 1981).…”

Effects of Mineralocorticoid and Glucocorticoid Receptor Blockade on Hypothalamic–Pituitary–Adrenal Function in Female Rats Prenatally Exposed to Ethanol

“…However, as E and PF animals often differ in HPA hyperresponsiveness, it is possible that a different mechanism may be mediating alterations in these 2 groups. Indeed, recent data suggest that hyperresponsiveness in E animals may be related primarily to alterations in CRH, whereas hyperresponsiveness in PF animals may primarily involve alterations in AVP (Lan et al, 2006;Zhang et al, 2005). Furthermore, as combined blockade of both MRs and GRs was not assessed, another possibility is that CORT feedback through 1 receptor subtype was able to compensate for blockade of the other subtype to maintain a normal ACTH response.…”

Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure

“…The liquid ethanol diet was introduced gradually over the first 3 days with bottles containing: G1 - 66% control diet, 34% ethanol diet; G2 - 34% control diet, 66% ethanol diet; G3-21 - 100% ethanol diet. This diet is formulated to provide adequate nutrition to pregnant rats regardless of ethanol intake (Lan et al, 2006). Pair-fed dams were offered a liquid control diet with maltose-dextrin isocalorically substituted for ethanol, in an amount matched to the consumption of an alcohol-fed partner (g/Kg body weight/day of gestation).…”