A ghrelin receptor agonist enhanced colorectal motility in both male and female rats, but females required approximately 10-fold higher doses — likely due to lower ghrelin receptor expression in the female lumbosacral spinal cord.
~10× dose differenceFemale rats required approximately tenfold higher doses of ghrelin agonist for equivalent colorectal motility response
What the researchers found
The ghrelin agonist RQ-00538053 enhanced colorectal motility in female rats but required ~10× higher doses than in males, correlating with lower ghrelin receptor expression in the female lumbosacral spinal cord.
Why it matters
Constipation disproportionately affects women. If ghrelin-based drugs for gut motility require sex-specific dosing, clinical trials and eventual prescribing must account for this biological difference — otherwise, women may be systematically underdosed.
The numbers in context
Approximately 10-fold higher doses needed in female vs. male rats for similar colorectal motility responses; tested via both intravenous and intrathecal routes.
How the study worked
Pharmacological study comparing intravenous and intrathecal (lumbosacral spinal cord) administration of ghrelin agonist RQ-00538053 in male and female Sprague-Dawley rats, with RT-qPCR analysis of ghrelin receptor expression.
Who was studied
Male and female rats
What this study cannot tell us
Animal study in rats — sex differences in ghrelin receptor expression may differ in humans. Only one ghrelin agonist tested. Sample size not specified in abstract. The mechanism is partially explained (receptor expression) but other factors (hormonal, metabolic) may contribute.
How to read the evidence
Moderate evidence — well-designed animal pharmacology study with mechanistic insight (receptor expression data). However, translation to human dosing is uncertain.
When this study was published
Published in 2024. Addresses an emerging area of sex-specific pharmacology in gut peptide therapeutics.
The bigger picture
Sex differences in drug response are increasingly recognized but still underappreciated in drug development. This study adds ghrelin receptor agonists to the growing list of therapeutics where biological sex significantly affects efficacy — reinforcing the need for sex-stratified clinical trials in gut motility disorders.
Questions still open
- Do human females also have lower ghrelin receptor expression in the lumbosacral spinal cord compared to males?
- Could estrogen or other sex hormones modulate ghrelin receptor expression in the spinal cord?
- Would sex-specific dosing of ghrelin agonists translate to better constipation outcomes in clinical trials?
Common questions
Why would a ghrelin drug work differently in males and females?
Could this affect future constipation medications?
Read the original research
Sexual dimorphism in prokinetic effects of a ghrelin agonist acting through the lumbosacral defecation center in rats.
The journal of physiological sciences : JPS, 74(1), 54
Citation
Tsukamoto, Shumpei; Sawamura, Tomoya; Yuki, Natsufu; Horii, Kazuhiro; Horii, Yuuki; Homma, Takeshi; Saito, Shouichiro; Shiina, Takahiko; Shimizu, Yasutake. (2024). Sexual dimorphism in prokinetic effects of a ghrelin agonist acting through the lumbosacral defecation center in rats.. The journal of physiological sciences : JPS, 74(1), 54. https://doi.org/10.1186/s12576-024-00949-w