Cholecystokinin, a Satiety Hormone, Regulates Gonadotropin Secretion and Reproduction in Fish

Core Concepts

Cholecystokinin, a satiety hormone, directly activates FSH cells and gates reproduction in fish by controlling the secretion of both gonadotropins, FSH and LH.

Abstract

The study reveals that in fish, the processes of folliculogenesis and ovulation are controlled by distinct neuropeptides - cholecystokinin (CCK) and gonadotropin-releasing hormone (GnRH), respectively.
Key highlights:

CCK receptor is highly expressed in FSH cells and CCK-producing neurons innervate the pituitary near FSH cells.
Mutating the CCK receptor leads to severe disruption of gonad development and an all-male population with underdeveloped testes, suggesting CCK is crucial for regulating both FSH and LH secretion.
Calcium imaging shows that GnRH preferentially activates LH cells, while CCK directly stimulates FSH cells.
The stimulated calcium activity of LH and FSH cells is associated with the secretion of their respective gonadotropin hormones.
The findings establish a direct neuroendocrine link between nutritional status and reproduction in fish, with CCK serving as the metabolic gate for gonadal development.

Stats

Gonad area of CCKR mutant zebrafish is significantly smaller compared to wildtype and heterozygous fish.
The distribution of cell types in the gonads of CCKR mutant zebrafish shows a significant reduction in the maturation of cells to spermatozoa.
Expression of both LH and FSH beta subunits is significantly decreased in the pituitary of CCKR mutant zebrafish.

Quotes

"CCK, a satiety hormone, directly activates FSH cells and gates reproduction in fish by controlling the secretion of both gonadotropins, FSH and LH."
"The findings establish a direct neuroendocrine link between nutritional status and reproduction in fish, with CCK serving as the metabolic gate for gonadal development."

Key Insights Distilled From

The satiety hormone cholecystokinin gates reproduction in fish by controlling gonadotropin secretion

by Hollander co... at www.biorxiv.org 06-21-2023

https://www.biorxiv.org/content/10.1101/2023.06.18.545454v3

Deeper Inquiries

How might the CCK-mediated regulation of gonadotropin secretion in fish be leveraged to improve aquaculture practices

The CCK-mediated regulation of gonadotropin secretion in fish presents an opportunity to enhance aquaculture practices in several ways. Firstly, understanding the role of CCK in controlling reproductive processes can lead to the development of novel strategies for manipulating gonadal development and reproduction in farmed fish. By targeting the CCK pathway, aquaculturists may be able to regulate the timing of ovulation and improve the efficiency of breeding programs. This could be particularly beneficial in species where reproductive success is crucial for commercial production.
Furthermore, leveraging the CCK-gonadotropin axis could help in optimizing feeding practices in aquaculture. Since CCK is a satiety hormone, its involvement in regulating reproduction based on nutritional status suggests that manipulating feeding regimes could influence gonadal development and spawning in fish. By understanding how CCK signaling interacts with feeding behavior and metabolic status, aquaculturists can tailor feeding schedules to optimize reproductive outcomes and overall fish health.
Additionally, the insights gained from studying the CCK pathway in fish could lead to the development of new hormone-based treatments or interventions to improve reproductive performance in aquaculture species. By targeting specific receptors or pathways involved in CCK signaling, aquaculturists may be able to enhance fertility, increase spawning rates, and improve the overall reproductive success of farmed fish populations.

What are the potential evolutionary advantages and disadvantages of having distinct neuropeptide regulators for folliculogenesis and ovulation in fish compared to the mammalian system

Having distinct neuropeptide regulators for folliculogenesis and ovulation in fish compared to the mammalian system offers both evolutionary advantages and disadvantages. One potential advantage is the fine-tuned control and specialization of reproductive processes. By having separate neuropeptides, fish can regulate folliculogenesis and ovulation independently, allowing for more precise control over the timing and coordination of these processes. This specialization may be particularly advantageous in species with complex reproductive strategies or environmental challenges.
On the other hand, the evolutionary disadvantage of this system may lie in its complexity and potential vulnerability to disruption. Having multiple neuropeptides involved in regulating reproductive processes increases the risk of dysregulation or malfunction, which could impact fertility and reproductive success. In contrast, the mammalian system, with a single neuropeptide (GnRH) controlling both folliculogenesis and ovulation, may offer a more streamlined and efficient regulatory mechanism.
Overall, the potential evolutionary advantages of distinct neuropeptide regulators in fish include specialized control over reproductive processes, while the disadvantages may involve increased complexity and susceptibility to disruption.

Could disruption of the CCK-gonadotropin axis play a role in reproductive disorders in other vertebrates beyond fish

Disruption of the CCK-gonadotropin axis could potentially play a role in reproductive disorders in other vertebrates beyond fish. The findings from the study on fish suggest that CCK is a crucial regulator of gonadotropin secretion and reproductive processes, linking metabolic status to fertility. If similar mechanisms exist in other vertebrates, alterations in CCK signaling could lead to reproductive disorders such as infertility, irregular ovulation, or impaired spermatogenesis.
For example, in mammals, disruptions in CCK signaling have been linked to metabolic disorders and gastrointestinal issues. If CCK also plays a role in regulating reproductive processes in mammals, disturbances in its function could impact fertility and reproductive health. Additionally, since CCK is involved in satiety and energy balance, changes in its signaling pathways could affect the allocation of resources towards reproduction, potentially leading to reproductive disorders.
Understanding the role of CCK in the gonadotropin axis and its potential impact on reproductive health in vertebrates could provide valuable insights into the mechanisms underlying fertility and may offer new avenues for investigating and treating reproductive disorders in humans and other mammals.