Reproductive experience (i.e. pregnancy, parturition and lactation) results in long lasting alterations in the female mammal's neural and endocrine systems. In the previous grant period, using a rat animal model, we demonstrated that reproductive experience alters circulating prolactin and estradiol levels, estradiol-stimulated prolactin secretion, neural prolactin receptor expression, and prolactin receptor transduction mechanisms. Significant effects of reproductive experience on anxiety-like behavior were also found in reproductively experienced animals during their subsequent reproductive cycles that were dependent upon the stage of the estrous cycle and the age of the female. Based on these findings, we propose to test the following hypothesis: "Reproductive Experience Induces a Fundamental Shift in the Neural Regulation of Hormone Secretion and Action in Female Mammals." We propose that this shift in hormone sensitivity is brought about in part by an up-regulation of prolactin receptor function in both neural and peripheral tissues that renders endocrine target tissues less dependent on circulating hormones. In addition, we propose that differential shifts in the sensitivities of estrogen receptor subtypes develop as a function of reproductive experience that alter the female's responses to estrogen. Specific studies will investigate the effects of reproductive experience on prolactin and estradiol receptor expression, prolactin transduction mechanisms, and shifts in estradiol and prolactin receptor sensitivity. Another experiment examines whether postpartum hyperprolactinemia and the age of reproductive experience contribute to the effects of reproductive experience on subsequent endocrine activity. Next, a series of studies investigate the impact of reproductive experience on anxiety, examining the hormonal regulation of anxiety within the context of the female's reproductive experience and how aging may interact with reproductive experience to affect anxiety. Finally, the possible effects of reproductive experience on non-neural endocrine target tissues, i.e. mammary tissue and liver, are examined to determine whether hormone receptor systems are altered in non-neural tissues as they are in the brain. Techniques used include real time RT-PCR, Western blot analysis, in situ hybridization, radioimmunoassay, and behavioral testing. The results of these studies should provide insight regarding the role of the hypothalamus in neuroendocrine plasticity and significant information regarding the transformative nature of reproductive experience. Most female mammals, including women, become pregnant and give birth one or more times over the course of their lifetimes. To date, little attention has been given to the long-term impact of this reproductive experience on the female's physiology and health later in adulthood. The present proposal uses a rodent model to examine this issue. Hormone levels, the responsiveness of the brain to hormones, and anxiety will be characterized following reproductive experience. The effects of reproductive experience on mammary gland and liver hormone receptors will also be compared with those in brain to determine the breath of established reproductive experience-induced changes. Overall, reproductive experience-induced shifts in endocrine activities may affect endocrine-related diseases and behaviors later in adulthood, i.e. breast cancer, autoimmune diseases, and postpartum mood disorders.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD039895-09
Application #
7996063
Study Section
Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
Program Officer
Lamar, Charisee A
Project Start
2000-12-01
Project End
2012-11-30
Budget Start
2010-12-01
Budget End
2011-11-30
Support Year
9
Fiscal Year
2011
Total Cost
$324,045
Indirect Cost
Name
Tufts University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
039318308
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 α activation. J Neuroendocrinol 25:1280-9
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
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
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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