# Project 2 - Role of Glycosylation in FSH Signaling in FSH Target Cells

> **NIH NIH P01** · WICHITA STATE UNIVERSITY · 2020 · $364,081

## Abstract

ABSTRACT
The perimenopausal period can last more than a decade and is attended by significant morbidity including
irregular reproductive cycles, dysfunctional uterine bleeding, urogenital changes, impaired fertility, declining
bone mass, vasomotor symptoms, and psychological impairment. The first sign of ovarian aging is a rise in
circulating FSH concentrations. We have identified that young women have high levels of hypo-glycosylated
FSH21 while older women have high levels of fully-glycosylated FSH24. The biological activity of hypo-
glycosylated FSH21 is much greater on the ovary where it binds efficiently to its receptor and stimulates estrogen
production and follicle development. In contrast, the fully-glycosylated FSH24 has lesser effects at the level of
the ovary, but has stimulatory effect on bone remodeling cells that promote osteoporosis. Thus, the changes in
FSH glycosylation associated with aging and their actions in both traditional (ovarian granulosa cells) and non-
traditional FSH target tissues (bone) requires immediate attention. The central hypothesis for this project is that
in the face of a senescing ovary, the additional switch of hypo- to fully-glycosylated FSH further compromises
reproductive potential and at the same time may hasten bone loss. The proposed Specific Aims will identify how
and why the age dependent differences in FSH glycosylation alter the function of ovarian follicles and bone, a
nontraditional FSH target. We will identify the specific intracellular signals that distinguish the action of hypo-
glycosylated hFSH21 from the age-related fully-glycosylated FSH24 isoform. Mechanistic studies will demonstrate
how these signals contribute to enhanced or reduced bioactivity in the ovary and bone. This project is innovative
because it studies for the first time the impact of naturally occurring FSH glycoforms on the function of aging
ovaries and on osteoclast formation in a nontraditional FSH target, bone. We are in an exclusive position to
establish the mechanism of action of these novel FSH glycoforms using in vivo and in vitro models and multiple
FSH target tissues. The impact of this work is that once we identify the unique biologic activities and functions
of FSH glycoforms, we can then use this knowledge to develop strategies to maintain ovarian function and limit
bone turnover. We have an outstanding team working in an outstanding environment, and have the tools
necessary to complete this exciting and important project. Understanding how the age-dependent change in
FSH glycoforms directs activities in multiple target tissue (ovary and bone) offers a unique opportunity to develop
novel approaches to improve fertility and reduce age associated morbidity. This proposal has translational
relevance that could be important for enhanced success for assisted reproductive technologies and the health
of pre- and post-menopausal women.

## Key facts

- **NIH application ID:** 9994172
- **Project number:** 5P01AG029531-09
- **Recipient organization:** WICHITA STATE UNIVERSITY
- **Principal Investigator:** JOHN S DAVIS
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $364,081
- **Award type:** 5
- **Project period:** 2009-04-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994172

## Citation

> US National Institutes of Health, RePORTER application 9994172, Project 2 - Role of Glycosylation in FSH Signaling in FSH Target Cells (5P01AG029531-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9994172. Licensed CC0.

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