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Prenatal Alcohol Exposure Alters Response of Kisspeptin‐ir Neurons to Estradiol and Progesterone in Adult Female Rats
Author(s) -
Sliwowska Joanna H.,
Bodnar Tamara S.,
Weinberg Joanne
Publication year - 2014
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12561
Subject(s) - kisspeptin , medicine , endocrinology , gonadotropin releasing hormone , arc (geometry) , luteinizing hormone , estrogen , hormone , biology , basal (medicine) , chemistry , geometry , mathematics , insulin
Background Prenatal alcohol exposure ( PAE ) has adverse effects on reproductive function and hypothalamic–pituitary–gonadal ( HPG ) activity. Kisspeptin neurons play a role in mediating feedback effects of estradiol ( E 2 ) and progesterone ( P 4 ) on the HPG axis. We hypothesized that PAE will have long‐term effects on the response of kisspeptin neurons to E 2 and P 4 . Methods Adult female rats (53 to 58 days) from prenatal ad libitum‐fed control ( C ), pair‐fed ( PF ), and alcohol‐exposed ( PAE ) groups were subjected to S ham ovariectomy ( OVX ) or OVX without or with replacement with low or high physiological levels of E 2 and P 4 , and terminated under basal conditions. E 2 and P 4 levels, and the response of kisspeptin‐ir neurons in the arcuate ( ARC ) and anteroventral periventricular ( AVPV ) nuclei to these hormones, were measured. As the E 2 signal is conveyed to kisspeptin neurons via estrogen receptor‐α ( ER ‐α), we investigated PAE effects on the number of kisspeptin‐ir/ ER ‐α‐ir neurons. To determine whether PAE alters interactions between kisspeptin and gonadotropin‐releasing hormone ( G n RH ) neurons, close contacts between kisspeptin‐ir fibers and G n RH ‐ir cell bodies were examined. Results Our data present the novel finding that kisspeptin‐ir neurons in the ARC of PAE females show differential responses to E 2 and to the combined treatment with E 2 and P 4 compared with controls: (i) OVX increased the number of kisspeptin‐ir neurons in C and PF , but not PAE females compared with their S ham counterparts; (ii) E 2 replacement restored kisspeptin‐ir cell numbers to S ham levels in C and PF females but caused a robust down‐regulation of kisspeptin‐ir neurons below S ham levels in PAE females; (iii) OVX and replacement with high physiological concentrations of E 2 resulted in fewer kisspeptin‐ir cells in PAE than C females; (iv) OVX and replacement with high levels of both E 2 and P 4 markedly decreased the number of kisspeptin‐ir neurons, below levels observed following E 2 alone, in PF and C females, but had no significant effect in PAE females. Conclusions These data suggest that a possible mechanism underlying adverse effects of PAE on HPG function involves actions of alcohol on the kisspeptin system.