Most adult female mammals are reproductively active and give birth once or multiple times. Surprisingly, little attention, however, has been given to the possible long-term effects of prior reproductive experience on endocrine and neural functions in adult females. The present proposal draws upon the finding that parity produces long-term alterations in circulating prolactin (PRL) and androgens in women, similar reductions in PRL secretion in reproductively experienced rats, and an increase in dopaminergic tone in both women and rats. The overall aim of this proposal is to characterize the extent and basis of the endocrine and neural changes induced by prior parity. The first series of studies will characterize the effects of parity on pituitary RL and estradiol secretion in parous and nulliparous female rats. The effects of parity on estrogen receptors and whether parity produces a reduction in estrogen feedback regulation on PRL will then be investigated. Next, the contribution of elevated PRL during lactation on its own secretion later in adulthood will be measured. The second series of experiments will determine how parity may increase dopaminergic function, an increase which may underlie the reductions in PRL secretion in parous animals. The effects of parity on dopamine receptors, second messengers that mediate dopamine action, and estrogenic regulation of dopamine release both in hypothalamic and extrahypothalamic areas (using an in vivo microdialysis system combined with HPLC) will be measured. The possible decrease in sensitivity of dopamine neurons to PRL regulation as a result of prior parity will then be evaluated. The third set of studies will examine whether the effects of parity on PRL secretion are age-dependent. The effects of the age of first parity on circulating estrogen levels late in adulthood and estrogen regulation of PRL secretion will be determined. Overall, these studies will identify underlying mechanisms which contribute to the alterations in endocrine and neural functions produced by a previous parity in the adult female, alterations which may affect a wide spectrum of biological processes, including behavior, reproductive fertility, immune function, and hormone secretion, over the life span of the female.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD039895-01A1
Application #
6383491
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
De Paolo, Louis V
Project Start
2001-07-01
Project End
2006-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
1
Fiscal Year
2001
Total Cost
$213,975
Indirect Cost
Name
Tufts University
Department
Other Basic Sciences
Type
Schools of Veterinary Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111
Bridges, Robert S (2016) Long-term alterations in neural and endocrine processes induced by motherhood in mammals. Horm Behav 77:193-203
Bridges, Robert S (2015) Neuroendocrine regulation of maternal behavior. Front Neuroendocrinol 36:178-96
Price, Anya K; Bridges, Robert S (2014) The effects of bromocriptine treatment during early pregnancy on postpartum maternal behaviors in rats. Dev Psychobiol 56:1431-7
Byrnes, E M; Casey, K; Carini, L M et al. (2013) Reproductive experience alters neural and behavioural responses to acute oestrogen receptor ? activation. J Neuroendocrinol 25:1280-1289
Sapsford, Tony J; Kokay, Ilona C; Ostberg, Lovisa et al. (2012) Differential sensitivity of specific neuronal populations of the rat hypothalamus to prolactin action. J Comp Neurol 520:1062-77
Byrnes, Elizabeth M; Casey, Kerriann; Bridges, Robert S (2012) Reproductive experience modifies the effects of estrogen receptor alpha activity on anxiety-like behavior and corticotropin releasing hormone mRNA expression. Horm Behav 61:44-9
Bridges, Robert S; Scanlan, Victoria F; Lee, Jong-O et al. (2011) Reproductive experience alters prolactin receptor expression in mammary and hepatic tissues in female rats. Biol Reprod 85:340-6
Byrnes, John J; Bridges, Robert S; Byrnes, Elizabeth M (2011) Amphetamine sensitization in reproductively experienced female rats. Neurosci Lett 502:168-72
Sjoeholm, Annika; Bridges, Robert S; Grattan, David R et al. (2011) Region-, neuron-, and signaling pathway-specific increases in prolactin responsiveness in reproductively experienced female rats. Endocrinology 152:1979-88
Byrnes, E M; Babb, J A; Bridges, R S (2009) Differential expression of oestrogen receptor alpha following reproductive experience in young and middle-aged female rats. J Neuroendocrinol 21:550-7

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