The goals are to determine if during lactation, plasticity in oxytocin (OT) neurons involves the proto-oncogene c-fos, and if this gene expression correlates with a rise in OT in cerebrospinal fluid (CSF). The physiological consequences of plasticity and whether they require OT or gamma-aminobutyric acid (GABA) will also be studied. This research has implications for reproduction, endocrinology and cancer. Plasticity is the formation of new and reversible synapses involving growth and adaptation of neurons. OT neurons in the magnocellular system undergo plasticity from mid-gestation through lactation. These changes in synaptic morphology can be produced by intracerebroventricular (icv) infusion of OT and are believed necessary for the synchronized firing of OT neurons during suckling. Expression of c-fos is postulated in synaptic remodeling of the OT neuron during lactation since this proto-oncogene has been associated with plasticity of other neural systems. We will examine, using conscious rats, whether changes in OT levels in CSF correlate with expression of c- fos or its encoded protein, fos, in OT neurons during gestation, lactation or suckling, or after infusion (icv) of OT. It is proposed further, that OT-induced changes in plasticity decrease the responsiveness of the OT neuron to osmotic stimulation during lactation by a mechanism involving the inhibitory neurotransmitter, GABA. New synapses on the OT neuron during lactation contain GABA and the GABA receptor protein increases in cells when expression of c-fos is stimulated by Metrazole. Therefore, using receptor agonists and antagonists we will examine whether the attenuated release of OT to osmotic stimulation during lactation requires OT or GABA. Also, we will determine in anesthetized virgin or lactating rats whether GABA or its antagonist alters the firing rate of OT neurons to osmotic stimulation or the threshold and maximal frequency at which OT is released by electrical stimulation of magnocellular neurons. Techniques will include: RIA of OT and vasopressin, push-pull perfusion of CSF, electrophysiological recording and stimulation of the magnocellular system, Northern blot, slot blot and in situ hybridization for assessing mRNA for c-fos, and immunoblot and immunocytochemistry for identifying fos protein.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD025498-03
Application #
3326636
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1990-02-01
Project End
1995-01-31
Budget Start
1992-02-01
Budget End
1993-01-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Summy-Long, J Y; Kadekaro, M (2001) Role of circumventricular organs (CVO) in neuroendocrine responses: interactions of CVO and the magnocellular neuroendocrine system in different reproductive states. Clin Exp Pharmacol Physiol 28:590-601
Summy-Long, J Y; Bui, V; Gestl, S et al. (1998) Effects of central injection of kyotorphin and L-arginine on oxytocin and vasopressin release and blood pressure in conscious rats. Brain Res Bull 45:395-403
Liu, H; Terrell, M L; Bui, V et al. (1998) Nitric oxide control of drinking, vasopressin and oxytocin release and blood pressure in dehydrated rats. Physiol Behav 63:763-9
Koehler-Stec, E M; Byers, A; Summy-Long, J Y (1998) Effects of chronic central infusion of oxytocin on the response of the magnocellular neuroendocrine system to osmotic stimulation. Pharmacology 56:101-10
Kadekaro, M; Liu, H; Terrell, M L et al. (1997) Role of NO on vasopressin and oxytocin release and blood pressure responses during osmotic stimulation in rats. Am J Physiol 273:R1024-30
Summy-Long, J Y; Gestl, S; Terrell, M L et al. (1997) Osmoregulation of the magnocellular neuroendocrine system during lactation. Am J Physiol 272:R275-88
Kadekaro, M; Harris, J; Freeman, S et al. (1995) Water intake and activity of hypothalamoneurohypophysial system during osmotic and sodium stimulation in rats. Am J Physiol 268:R651-7
Koehler, E M; McLemore, G L; Martel, J K et al. (1994) Response of the magnocellular system in rats to hypovolemia and cholecystokinin during pregnancy and lactation. Am J Physiol 266:R1327-37
Summy-Long, J Y; Neumann, I; Terrell, M L et al. (1994) Crosstalk in the magnocellular system during osmotic stimulation of one supraoptic nucleus. Brain Res Bull 33:645-54
Neumann, I; Koehler, E; Landgraf, R et al. (1994) An oxytocin receptor antagonist infused into the supraoptic nucleus attenuates intranuclear and peripheral release of oxytocin during suckling in conscious rats. Endocrinology 134:141-8

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