# PROJECT 1 - Age-Related Changes in Gonadotropin Glycosylation and Function

> **NIH NIH P01** · WICHITA STATE UNIVERSITY · 2020 · $315,838

## Abstract

Our long-term goal is to understand how carbohydrate modulates the biological activity of follicle-
stimulating hormone (FSH). The human ovary becomes resistant to FSH stimulation with age and circulating
FSH concentrations rise, keeping serum estrogen concentrations normal until 2 years before the final
menstrual cycle. Around the same time, pituitary FSH changes from predominantly hypo-glycosylated hFSH21
(due to loss of at least one FSHβ subunit N-glycan) to a predominantly fully-glycosylated hFSH24, which
possesses all 4 N-glycans. Hypo-glycosylated hFSH21 exhibits greater apparent affinity for the FSHR, can
occupy more FSHR sites, and associates with FSHR more quickly than fully-glycosylated hFSH24. The overall
hypothesis of this proposal is that in the face of a senescing ovary the additional switch from hypo-glycosylated
FSH21 to fully-glycosylated FSH24 further compromises fertility and may affect bone. The objectives of this
proposal are to study mechanisms for differences in FSHR binding and develop tools to measure FSH
glycoform ratios via the following specific aims: 1: Evaluate the roles of FSHR oligomerization and FSH
glycosylation on FSH binding site access. Our working hypothesis is that hFSH21 or allosteric modulator
binding can change the conformation of FSHRs, thereby increasing the number of available binding sites for
FSH24. The resulting greater FSHR occupancy will provoke a correspondingly larger response in gonadal
target cells. In aging, hFSH21 abundance decreases, fewer FSHRs are occupied and cellular stimulation is
attenuated. 2: Evaluate FSH glycoform abundance as a potential infertility marker. Our working
hypothesis is that the hFSH21 to hFSH24 ratio changes during normal physiological events, such as the
menstrual cycle and aging. Isolation of both 21k-FSHβ and 24k-FSHβ subunit glycoforms enhances our ability
to elicit glycoform-specific antibodies. Glycoform-specific assays can measure changes in circulating glycoform
ratios to define their roles in reproductive physiology. 3. Study the clearance and tissue distribution of
FSH21 and FSH24 in the mouse. Our working hypothesis is that FSH21 will be cleared from the circulation more
rapidly than FSH24, yet the same mechanism will deliver more FSH21 to target tissues. In bone, where FSH24 is
active and FSH21 less active or inactive, FSH24 may preferentially accumulate.
 The potential translational outcomes of this project include identifying a better diagnostic marker,
altered hFSH21/hFSH24 ratio, for reproductive aging diagnosis, and methods to increase the effectiveness of
existing pharmaceutical FSH preparations.

## Key facts

- **NIH application ID:** 9994169
- **Project number:** 5P01AG029531-09
- **Recipient organization:** WICHITA STATE UNIVERSITY
- **Principal Investigator:** GEORGE R BOUSFIELD
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $315,838
- **Award type:** 5
- **Project period:** 2009-04-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994169

## Citation

> US National Institutes of Health, RePORTER application 9994169, PROJECT 1 - Age-Related Changes in Gonadotropin Glycosylation and Function (5P01AG029531-09). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9994169. Licensed CC0.

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