Discovery and Characterization of an Endogenous Inhibitor of Soluble Adenylyl Cyclase

NIH RePORTER · NIH · F31 · $46,752 · view on reporter.nih.gov ↗

Abstract

Access to contraceptives and understanding mechanisms of infertility are key aspects of robust reproductive health. Unfortunately, existing contraceptive methods are not suitable or convenient for everyone, and the options for men are severely limited. In addition, while infertility is recognized as a disability carrying many negative consequences, it is not well understood; it is estimated that 50% of male infertility cases have an unknown etiology. Elucidating sperm functions and gaining a better understanding of sperm biology may shed light on these areas. Soluble adenylyl cyclase (sAC, ADCY10) is essential for sperm function and fertilization. I have uncovered the existence of a previously unappreciated mechanism for regulating sAC activity; an endogenous small molecule inhibitor of sAC. In this proposal, I will molecularly identify the endogenous inhibitor, determine its mechanism of inhibiting sAC, and explore its physiological significance by examining the distribution of the endogenous inhibitor in somatic tissues and male gametes. These studies propose to identify the first known physiological regulator that decreases sAC activity which will expand our knowledge of sAC. Gaining a better understanding of the endogenous inhibitor could provide a potential lead compound for the development of a non-hormonal male contraceptive and determining whether its levels change pathophysiologically may reveal new mechanisms of infertility.

Key facts

NIH application ID
10456053
Project number
5F31HD105363-02
Recipient
WEILL MEDICAL COLL OF CORNELL UNIV
Principal Investigator
Jacob Ferreira
Activity code
F31
Funding institute
NIH
Fiscal year
2022
Award amount
$46,752
Award type
5
Project period
2021-07-01 → 2024-06-30