Today we’re highlighting one of our saporin conjugates, Kisspeptin-SAP. This is a tool for eliminating cells that express the human and sheep G-protein coupled receptor, GPR54.
Kisspeptin is a ligand to GPR54 and functions in the hypothalamus, placenta, liver, pancreas, adipose tissue, bone, and limbic regions which shows the importance it can play in diagnosis and treatment of various disorders. It is one of the neuropeptides that governs the reproductive endocrine axis by regulating neuronal activity and secretion of hypothalamic gonadotropin releasing hormone (GnRH). GnRH is released from the hypothalamus to act on the anterior pituitary triggering the release of luteinizing hormone (LH), and follicle stimulating hormone (FSH). These gonadotropic hormones lead to sexual maturation and gametogenesis.
This is a 2023 publication using a Kisspeptin-saporin conjugate.
The objective of the authors was to test the functional role of ovine KNDy neurons in pulse generation and identify the roles of nearby Kiss1 receptor (Kiss1R)-containing cells. They performed these tests using conjugates NKB-SAP and Kisspeptin-SAP.
The results showed that NKB-SAP ablated over 90% of the KNDy cells, while Kisspeptin-SAP lesioned about two-thirds of the Kiss1R population. This led to a significant decrease in LH pulse amplitude and altering LH pulse patterns. NK3-SAP increased the interpulse interval without affecting the regularity of LH pulses, whereas Kiss-SAP disrupted their regular hourly occurrence but not the interpulse interval.
These findings suggest that KNDy neurons are critical for GnRH pulse generation in ewes, while ARC Kiss1R cells support the amplitude and regularity of these pulses, possibly as part of a positive feedback loop involving GABA or glutamate.
