Related Experiment Video
Updated: Mar 19, 2026
09:39
Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
Published on: January 27, 2014
13.1K
Targeting Soluble Adenylyl Cyclase for On-Demand Contraception
Erin R Gardner1, Gregory S Kopf2, Jochen Buck3
1Gardner Pharmacology, LLC, Vienna, Virginia, United States.
Physiology (Bethesda, Md.)
|March 17, 2026
Summary
Soluble adenylyl cyclase (sAC) is crucial for sperm function and male fertility. Inhibiting sAC offers a potential nonhormonal contraceptive approach by reducing sperm motility.
Area of Science:
- Biochemistry
- Reproductive Biology
- Pharmacology
Background:
- Soluble adenylyl cyclase (sAC; ADCY10) is an intracellular cAMP source distinct from transmembrane adenylyl cyclases.
- sAC is highly expressed in male germ cells and regulated by bicarbonate and calcium.
- sAC is essential for male fertility, with its loss causing immotile sperm and infertility.
Purpose of the Study:
- To explore sAC as a target for nonhormonal, on-demand male contraceptives.
- To evaluate the potential of sAC inhibition for fertility control.
Main Methods:
- Genetic and pharmacological studies in rodents and humans.
- In vivo studies using a proof-of-concept sAC inhibitor in mice.
Main Results:
- sAC activity is essential for sperm motility and fertilization.
- A proof-of-concept sAC inhibitor demonstrated rapid, reversible contraceptive effects in mice.
- Challenges for clinical translation include defining efficacy onset/duration and ensuring post-ejaculation sperm inactivation.
Conclusions:
- sAC is a promising target for novel male contraceptive development.
- On-demand sAC inhibitors could offer a nonhormonal approach to fertility control.
- Further research is needed to address clinical translation challenges for on-demand male contraception.
Related Concept Videos
01:09GPCRs Regulate Adenylyl Cylase Activity
8.1K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
8.1K
01:30Adrenergic Agonists: Direct-Acting Agents
3.1K
Drugs that mimic the action of endogenous catecholamines like noradrenaline and adrenaline are called adrenergic agonists or sympathomimetics. Based on their mechanism of action, sympathomimetics can be classified as direct-, indirect-, or mixed-acting sympathomimetics. Direct-acting adrenergic agonists activate adrenoceptors without affecting presynaptic neurons, making them independent of neuronal catecholamine-depleting agents like reserpine and guanethidine.
These agents can be classified...
These agents can be classified...
3.1K
01:21Intrauterine Drug Delivery Systems
101
Controlled-release systems for intravaginal and intrauterine drug delivery have been developed primarily for the administration of contraceptive steroid hormones. These delivery routes circumvent first-pass hepatic metabolism, thereby enhancing bioavailability and allowing for reduced systemic dosages compared to oral administration. Such approaches contribute to improved therapeutic efficacy and patient compliance, particularly in long-term contraceptive regimens.Intravaginal Drug Delivery...
101
01:27Transducer Mechanism: Enzyme-Linked Receptors
4.7K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
4.7K
01:26Secondary Messengers in Hormone Action
6.0K
Water-soluble hormones cannot cross the plasma membrane, so they rely on protein receptors that span the membrane to trigger intracellular signaling pathways. These pathways then activate second messengers inside the cell, including cAMP or calcium ions.
Many hormones bind to transmembrane G protein-coupled receptors that connect to regulatory G proteins. These G proteins can then activate enzymes such as adenylyl cyclase or phospholipase C. Adenylyl cyclase converts ATP to cAMP, activating...
Many hormones bind to transmembrane G protein-coupled receptors that connect to regulatory G proteins. These G proteins can then activate enzymes such as adenylyl cyclase or phospholipase C. Adenylyl cyclase converts ATP to cAMP, activating...
6.0K
01:22Birth Control Methods
7.1K
Vasectomy is a surgical form of male sterilization that involves severing and sealing the vasa deferentia, preventing sperm from mixing with semen during ejaculation. Because a vasectomy does not impact the testes' ability to produce testosterone, hormone levels, libido, and sexual function generally remain unchanged. While vasectomy is highly effective in preventing pregnancy, with a success rate near 99.85%, rare cases of recanalization (spontaneous reconnection) can occur. Although...
7.1K