Coitus induces a concatenation of neurohumoral events in New Zealand White rabbits that includes increased secretion of norepinephrine (NE), gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), ovarian steroids, and finally the release of ova. Brainstem neurons that synthesize NE are a likely component of the signaling pathway as enhanced expression of tyrosine hydroxylase (TH) and NE transporter (NET) mRNAs occurs by 15-min postcoitus in locus coeruleus (LC), while intrahypothalamic infusion of either prazosin (alpha1 adrenergic blocker) or desipramine (NET blocker) alters the GnRH/LH surge. The P.I. proposes three new aims to extend the understanding of this neurochemical process.
Aim 1 would identify neurotransmitters and neuronal circuits that relay coital signals to the LC and/or hypothalamus. Neuropeptide Y (NPY) mRNA expression was not observed in the rabbit LC; however, TH, NPY and/or NET mRNAs were co-localized in the paragigantocellularis (nPGi) or praepositus hypoglossi (nPH) nuclei--two brainstem nuclei that innervate the LC. The P.I. hypothesizes that vaginal signals reach the nPGi and/or nPH where they excite interneurons (i.e., NPY, acetylcholine [ACH]) that either stimulate the NE/NET neurons in LC or project directly to hypothalamic cells.
Aim 1 a will identify by in situ hybridization (ISH) cfos-labeled brainstem neurons for evidence of early postcoital activated cells.
Aim 1 b will identify cells for TH, NET, NPY, NPY receptors, ACH esterase (Ache) and glutamic acid decarboxylase (GAD) in the LC, nPGi and nPH by ISH.
Aim 1 c will define the specific cell types after coitus that dual stain for the above and also express cFos protein (ISH for mRNAs, immunocytochemistry for cFos protein).
Aim 2 will examine if ACH and gamma aminobutyric acid (GABA) affect the postcoital GnRH/LH surge by action through brainstem/hypothalamic connections. The P.I. will administer a specific ACH blocker ( alpha-conotoxin) and GABAA agonist (muscimol) either locally into the hypothalamus or into the 4th ventricle near brainstem-relevant neurons. Mating-induced GnRH/LH secretion and brainstem TH/NET/NPY mRNAs will be measured in rabbits with and without drug treatment.
Aim 3 will target brainstem loci by either microinjection of antisense oligonucleotides or electrical lesioning.
Aim 3 a will decipher if administration of TH or NET antisense oligonucleotides into the LC blocks the coital-induced NE/GnRH release.
Aim 3 b will determine if electrical lesions of the nPGi and/or nPH prevent either the postcoital expression of LC cFos protein, TH/NET mRNAs or the LH surge. These studies may provide information on neurologically related infertility.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD030316-06
Application #
6181524
Study Section
Reproductive Endocrinology Study Section (REN)
Program Officer
De Paolo, Louis V
Project Start
1994-07-15
Project End
2002-03-31
Budget Start
2000-04-01
Budget End
2002-03-31
Support Year
6
Fiscal Year
2000
Total Cost
$218,481
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Other Domestic Higher Education
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Centeno, Maria Luisa; Henderson, Jessica A; Pau, K-Y Francis et al. (2006) Estradiol increases alpha7 nicotinic receptor in serotonergic dorsal raphe and noradrenergic locus coeruleus neurons of macaques. J Comp Neurol 497:489-501
Centeno, Maria Luisa; Luo, Jie; Lindstrom, Jon M et al. (2004) Expression of alpha 4 and alpha 7 nicotinic receptors in the brainstem of female rabbits after coitus. Brain Res 1012:1-12
Bao, J; Pau, K Y; Spies, H G (2001) Norepinephrine transporter mRNA expression after coitus in the rabbit brainstem. Chin J Physiol 44:103-10
Pau, C Y; Pau, K Y; Berria, M et al. (2000) Ovarian influence on gonadotropin and prolactin release in mated rabbits. Endocrine 13:25-35
Caba, M; Pau, K Y; Beyer, C et al. (2000) Coitus-induced activation of c-fos and gonadotropin-releasing hormone in hypothalamic neurons in female rabbits. Brain Res Mol Brain Res 78:69-79
Caba, M; Bao, J; Pau, K Y et al. (2000) Molecular activation of noradrenergic neurons in the rabbit brainstem after coitus. Brain Res Mol Brain Res 77:222-31
Yang, S P; Pau, K Y; Airhart, N et al. (1998) Attenuation of gonadotropin-releasing hormone reflex to coitus by alpha1-adrenergic receptor blockade in the rabbit. Proc Soc Exp Biol Med 218:204-9
Pau, K Y; Lee, C J; Cowles, A et al. (1998) Possible involvement of norepinephrine transporter activity in the pulsatility of hypothalamic gonadotropin-releasing hormone release: influence of the gonad. J Neuroendocrinol 10:21-9
Pau, K Y; Spies, H G (1997) Neuroendocrine signals in the regulation of gonadotropin-releasing hormone secretion. Chin J Physiol 40:181-96
Yang, S P; Pau, K Y; Spies, H G (1997) Tyrosine hydroxylase and norepinephrine transporter mRNA levels increase in locus coeruleus after coitus in rabbits. J Mol Endocrinol 19:311-9

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