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Open Access Knowledge and Scholarship

Date of Award

6-2010

Culminating Project Type

Thesis

Degree Name

Biological Sciences - Cell and Molecular: M.S.

Department

Biology

College

College of Science and Engineering

First Advisor

Oladele Gazala

Second Advisor

Gordon Schrank

Third Advisor

Maureen Tubbiola

Fourth Advisor

David Bacharach

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

Keywords and Subject Headings

Gut motility, sex differences, brain, reproduction

Abstract

Undernutrition markedly inhibits reproduction in mammals; however, the mechanisms by which the metabolic status is linked to the reproductive axis remains unclear. Gut-derived factors have been implicated in the central regulation of several physiological processes. Motilin, a peptide produced in the gastrointestinal tract, is secreted during the interdigestive period, and has been implicated in several processes such as inducing the migrating myoelectric complex or inhibiting luteinizing hormone (LH) secretion by mechanisms not presently determined. The objective of the studies presented in this thesis was to determine the effects of administration of exogenous motilin on the secretion of gonadotropin-releasing hormone (GnRH) by hypothalamic explants obtained from male and female Sprague-Dawley rats. To that purpose, hypothalami were obtained post-euthanasia from male, ovariectomized (OVEX) or OVEX implanted with an estradiol mini-pumps (OVEX+E2) rats, and incubated in artificial cerebrospinal fluid (aCSF) using a shaking water bath. After one hour of equilibration, 600 μI of spent medium were harvested every 7.5 minutes and replaced with the same volume of fresh aCSF for a total of 60 minutes. After that time, 1.4 ng motilin/600 μI or 2.5 ng motilin/600 μI were added to the bath, and sampling continued at the same frequency for 120 minutes. During the last 60 minutes of the experiment 75 mM N-methyl-D-aspartate (NMDA) was added to the bath in order to confirm the viability of the • hypothalamic extracts. Results indicated that in vitro secretion of GnRH remained pulsatile along the experiment. Our results indicate that administration of motilin did not inhibit hypothalamic GnRH secretion in male, OVEX and OVEX+E2 rats. As expected, plasma concentrations of LH were significantly elevated in OVEX rats when compared to the rest of experimental animals, and plasma levels of estradiol were significantly greater in OVEX+E2 rats than in the other animal groups. Based on our in vitro studies, the effects of exogenous motilin on inhibiting LH secretion may .be hypothalamus-independer1t, through direct effects on the pituitary gland or through other cerebral neurotransmitter systems.

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