# EPIDIDYMAL GLUTATHIONE--PHYSIOLOGIC & MOLECULAR STUDIES

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 1994 · $118,700

## Abstract

As spermatozoa progress along the epididymal duct, they are bathed in a
specialized luminal fluid microenvironment which is crucial for their
maturation and survival.  As the spermatozoa mature, they need constant
protection against oxidative damage and from harmful effects of drugs and
toxic chemicals.  Damaged spermatozoa may lead to abnormal offspring.  In
many tissues such as the lung and kidney, glutathione (glu-cys-gly) has
been shown to play an important role in antioxidant defense, and it seems
likely that it plays a similar role in the epididymis.  The focus of this
proposal is to determine the manner by which luminal glutathione is
regulated by the epididymal epithelium.  We will use in vivo micropuncture
and microperfusion techniques to determine the origin of glutathione in the
luminal fluid of different epididymal regions.  We will determine the
activity of gamma-glutamyl transpeptidase (GGT), the only known enzyme that
can cleave glutathione to yield glutamate and the dipeptide cysteine-
glycine.  Experiments will also be performed to determine the catalytic
activity of dipeptidase which cleaves cysteine-glycine into its constituent
amino acids.  The hypothesis that GGT can transport cysteine and glycine
from the lumen into the epididymal cells will be tested.  We have
previously found that luminal GGT catalytic activity declines from caput to
cauda.  Therefore, experiments will be designed to determine the
mechanism(s) of the loss of GGT activity within the cauda epididymal
region, whether it is due to degradation of the enzyme by proteases and/or
endoglycosidases located within the luminal fluid and/or on the apical
surface of cauda epithelial cells.  Using molecular biological techniques
we will identify the epididymal cell type(s) that express GGT mRNA.  Hence,
we will identify those cells that play an important role in the regulation
of epididymal glutathione.  It is critical that we understand the
mechanisms by which the epididymis maintains an environment that will
protect spermatozoa from oxidation and from harmful effects of various
drugs and xenobiotics; oxidative defense is crucial for the survival of
spermatozoa.  This proposal is part of a long term goal to understand the
mechanisms by which the epididymis maintains an optimal luminal
microenvironment for sperm maturation and survival.  The findings from this
proposal will also provide fundamental information for the development of a
male contraceptive and treatment of certain forms of male infertility.

## Key facts

- **NIH application ID:** 2197612
- **Project number:** 5R01HD018257-09
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **SAM.gov UEI:** JJG6HU8PA4S5
- **Principal Investigator:** Barry T. Hinton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $118,700
- **Award type:** 5
- **Project period:** 1983-12-01 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197612

## Citation

> US National Institutes of Health, RePORTER application 2197612, EPIDIDYMAL GLUTATHIONE--PHYSIOLOGIC & MOLECULAR STUDIES (5R01HD018257-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197612. Licensed CC0.

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