# ROLE OF METALLOPROTEINASES IN OVARIAN FUNCTION

> **NIH NIH R29** · UNIVERSITY OF KENTUCKY · 1993 · $92,567

## Abstract

The proposed studies will provide basic information and improve our
understanding regarding the control and cellular origin of collagenase and
gelatinase activity during follicular development and ovulation as well as
during the life span of the corpus luteum. The goal of this proposal is to
investigate the changes and regulation of the ovarian metalloproteinases
collagenase and gelatinase and an associated inhibitor during the
reproductive cycle of the rat. Using biochemical, immunohistochemical, and
in vitro techniques, the present experiments are designed to determine: 1)
if the activities of collagenase, gelatinase and the inhibitor change
during cycles of ovarian connective tissue remodeling; 2) if enzyme and
inhibitor activities are hormonally regulated and what specific hormones
stimulate activity; 3) the physiochemical characteristics of the inhibitor
and whether it is serum or tissue-derived; and 4) the cellular location and
quantitative changes in collagenase during the follicular and luteal
periods. The first aspect of this study will use biochemical analyses to
examine the Changes in the activities of collagenase, gelatinase, and a
metalloproteinase inhibitor in ovaries collected during follicular and
luteal development in vivo. Second, the role of gonadotropins, cyclic
nucleotides, prostaglandins, and steroids in regulating collagenase,
gelatinase, and inhibitor activity will be studied in vitro with a
granulosa and luteal cell culture model and in vivo following intrabursal
administration. Third, the inhibitor's physiochemical properties will be
characterized. We will expand our exciting preliminary observations which
confirm the existence of an inhibitor and determine whether the inhibitor
has the characteristics of tissue inhibitors of metalloproteinases observed
in other tissues. The final goal of this investigation will be to elucidate
the cellular origin and changes in collagenase localization during
follicular development and rupture and during luteal formation and
regression by immunohistochemistry.

The information derived from the proposed studies will provide insight into
the basic mechanisms of ovarian connective tissue remodeling and may
ultimately lead to better methods for promoting or inhibiting follicular
rupture and luteal function. Although these studies are limited to the rat,
the findings may in the future be applicable to the human and relevant to
abnormalities such as luteinized unruptured follicles where the steroidal
environment is altered and proteolytic breakdown does not occur.
Furthermore, the information from the proposed research may be of
significance beyond reproductive physiology since metalloproteinases have
been implicated in a number of pathological processes such as arthritis and
tumor growth.

## Key facts

- **NIH application ID:** 2198787
- **Project number:** 5R29HD023195-05
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **SAM.gov UEI:** H1HYA8Z1NTM5
- **Principal Investigator:** Thomas E Curry
- **Activity code:** R29 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $92,567
- **Award type:** 5
- **Project period:** 1989-08-01 → 1996-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198787

## Citation

> US National Institutes of Health, RePORTER application 2198787, ROLE OF METALLOPROTEINASES IN OVARIAN FUNCTION (5R29HD023195-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198787. Licensed CC0.

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