Date of Degree

1998

Document Type

Dissertation

Degree Name

Ph.D.

Program

Biology

Advisor

Martin P. Schreibman

Committee Members

Dan Eshel

Paul F.A. Maderson

Shailesh P. Banerjee

Marlene Schwanzel-Fukuda

Subject Categories

Biology

Abstract

The N-methyl-D-aspartate type of glutamate receptor (NMDAR) is involved in the regulation of many neural functions, including neuroendocrine modulation of the vertebrate brain-pituitary-gonad axis. We have used a freshwater teleost, the platyfish (Xiphophorus maculatus), to document age- and gender-specific variations in NMDAR properties. We first localized immunoreactive (ir-) NMDAR in male and female platyfish brain at four stages of the lifespan. Distribution was limited to cells of the nucleus olfactoretinalis (NOR), a gonadotropin releasing hormone-containing nucleus. The number of ir-NMDAR cells was increased in pubescent and mature females when compared to immature and senescent animals. In males, there was no significant change in ir-NMDAR expression in the NOR at any time in their lifespan. The affinity of the antagonist MK-801 for the NMDA receptor, an indicator of subunit composition, was increased only in pubescent females. Maximum binding of MK-801 to NMDAR also varied with female development, reaching a significant maximum in mature females. In males, both maximum MK-801 binding and MK-801 affinity remained unchanged throughout development. Chronic injections of MK-801 to immature male and female platyfish resulted in a dose-dependent decrease in both the number of females in puberty and in their average size. Male puberty and growth were unaffected. Radioimmunoassay indicated an increased GnRH content in brain extracts from MK-801 treated females and no effect on GnRH content in treated males. Histological analysis showed decreased size of the gonadotropic zone in the anterior pituitary gland of treated females. There was no evidence that MK-801 directly influences the gonads. These studies are the first evidence of a sexually dimorphic relationship between the timing of NMDA receptor dynamics and neuroendocrine activity in the brain-pituitary gonad axis.

Comments

Digital reproduction from the UMI microform.

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