Abstract
Background
There is substantial evidence for sex differences in the functioning of one of the most common receptor systems; G protein-coupled receptors (GPCRs). There are many points along the GPCR-mediated molecular signaling pathway at which males and females may differ, one of the first of which, chronologically, is in the stability of the interaction between the ligand and the receptor, or its binding affinity. Here we investigate the binding affinities of oxytocin (OT) and vasopressin (AVP) at the oxytocin receptor (OTR) and the vasopressin V1a receptor (V1aR), both of which are present in numerous in brain regions associated with social behavior.
Method
In order to investigate sex- and estrous cycle-dependent differences in ligand-receptor binding affinity, male (n = 6) Syrian hamsters (Mesocricetus auratus), females on the day of estrus (E females, n = 6), and females on the second day of diestrus (D2 females n = 6) were chosen for study. Brains from hamsters were mounted on slides and competition and saturation binding assays were conducted.
Results
We report a remarkable similarity in the binding affinities of OT and AVP in males and females. Small differences were detected, however, in receptor and ligand specificity in females depending on whether they were in the estrous or diestrous stage of their ovulatory cycle.
Conclusion
These data suggest that sex differences in binding affinity are not a likely source of the many sex differences that have been observed in the effects of OT and AVP in hamsters and other species.
Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author upon reasonable request.
Abbreviations
- GPCR:
-
G protein-coupled receptor
- OT:
-
Oxytocin
- OTR:
-
Oxytocin receptor
- AVP:
-
Arginine vasopressin
- V1aR:
-
Vasopressin V1a receptor
- NSB:
-
Nonspecific binding
- D2:
-
Diestrus day 2
- E:
-
Estrus
- CRFr:
-
Corticotrophin releasing factor receptor
- DPM:
-
Disintegrations per minute
- [125I]OVTA:
-
[125I] ornithine vasotocin analogue
- [125I]LVA:
-
[125I] linear vasopressin antagonist
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Funding
This work was supported by NIH grant R01MH122622 to HEA.
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JHT designed and conducted all experiments, analyzed the data, and wrote the first draft of this manuscript. HEA supervised all aspects of the study, especially experimental design, data analysis, and preparation of the final submission.
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Taylor, J.H., Elliott Albers, H. Are there sex differences in oxytocin and vasopressin V1a receptors ligand binding affinities?. Pharmacol. Rep 76, 416–423 (2024). https://doi.org/10.1007/s43440-024-00577-6
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DOI: https://doi.org/10.1007/s43440-024-00577-6