The role of insulin-like growth factor-I and growth factor-associated signal transduction pathways in estradiol and progesterone facilitation of female reproductive behaviors.
We are examining the role of insulin-like growth factor-I (IGF-I) and downstream signal transduction pathways associated with growth factors (e.g., mitogen-activated protein kinase, MAPK) in estradiol and progesterone facilitation of female reproductive behavior in rats. Brain IGF-I receptor activity is required for the long-term, priming actions of estradiol on the female reproductive axis. Infusions of an IGF-I receptor antagonist during estradiol priming blocks induction of hypothalamic alpha(1B)-adrenergic receptors and luteinizing hormone surges, and attenuates lordosis behavior. Infusion of MAPK and phosphatidylinositol-3-kinase inhibitors inhibitors during estradiol priming completely blocks hormone-facilitated lordosis. Because progestin receptors (PRs) can be phosphorylated and activated by MAPKs, growth factor signaling pathways may also participate in progesterone facilitation of reproductive behaviors. Infusion of a MAPK inhibitor in estradiol-primed rats blocks progestin facilitation and sequential inhibition of lordosis and proceptive behaviors. Interference with MAPK signaling also inhibits behavioral responses to cGMP and a delta-opioid agonist, both of which can activate MAPK in some cells. Thus MAPK is involved in the facilitation of lordosis and proceptive behaviors, perhaps by phosphorylation of hypothalamic PRs.
Etgen
Anne M
AM
Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA. etgen@aecom.yu.edu
González-Flores
Oscar
O
Todd
Brigitte J
BJ
D000818:Animals; D006152:Cyclic GMP / Q000502:physiology; D004958:Estradiol / Q000502:physiology*; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D016501:Neurites / Q000502:physiology; D009490:Neurosecretory Systems / Q000502:physiology; D011187:Posture; D011374:Progesterone / Q000502:physiology*; D051381:Rats; D011960:Receptors, Estrogen / Q000502:physiology; D017465:Receptors, Opioid, delta / Q000502:physiology; D012098:Reproduction / Q000502:physiology*; D012726:Sexual Behavior, Animal / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D011960:Receptors, Estrogen; D017465:Receptors, Opioid, delta; D011374:Progesterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D020928:Mitogen-Activated Protein Kinases; D006152:Cyclic GMP