The Rigakubu News

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Peptides in the brain regulate testicular function.

Chie Matani, Assistant Professor, Tokyo University of Agriculture and Technology*.

Most vertebrates have two sexes, female and male. Females produce eggs in the ovaries and males produce sperm in the testes. The development and maintenance of ovarian and testicular function are thought to be regulated by specific neural circuits in the brain and hormone secretion controlled by these circuits. In mammals, since the discovery of gonadotropin-releasing hormone ( GnRHNote 1 ) by Roger Guillemin and Andrew Wictor Schally in the 1970s, neurons in the brain that release GnRH Since Schally discovered gonadotropin-releasing hormone (GnRHNote 1), GnRH-releasing neurons in the brain are thought to play an important function in gonad development. In other words, GnRH released from GnRH neurons acts on the pituitary gland, which releases gonadotropic hormone into the blood, and this hormone acts on the ovaries and testes via blood circulation to cause the development of these gonads. However, many mysteries remain concerning the morphology of the testes and the mechanism in the brain for continued sperm production in vertebrates other than mammals, as it has been reported that male medaka fish with loss of GnRH function have normal reproductive function.

In this study, we focused on neuropeptidesNote 2) that are expressed in the brain and are thought to regulate neural activity, and created a male medaka fish in which the function of neuropeptide FF (Neuropeptide FF, NPFF), a type of neuropeptide, was lost using genome editing technology. We analyzed the morphology and function of the testes of male medaka with loss of NPFF function and found that the testes regress after sexual maturity, making it increasingly difficult for the medaka to leave a next generation of offspring. We also analyzed the expression of follicle-stimulating hormone (FSH), a gonad-stimulating hormone, in tissues where NPFF and its receptor proteins are expressed and whether the loss of NPFF function affects the expression of FSH. The results showed that in male medaka, NPFF released from neurons in the terminal nerve in the brain is received by NPFF receptor-expressing neurons in the preoptic area, and that FSH gene expression in the pituitary gland is upregulated by some signals released from these neurons, thereby maintaining testis morphology and This finding suggests that the function of spermatogenesis and testicular morphology is maintained by the upregulation of FSH gene expression in the pituitary gland via some signal released from these neurons (Figure). This finding is expected to advance our understanding of the mechanisms in the brain that control the development and function of fish testes, which are still poorly understood, and to lead to research for the improvement of aquaculture methods.

Figure: Working hypothesis on the mechanism by which NPFF is involved in the maintenance of testicular morphology and function.

NPFF released from neurons in the terminal nerve is received by neurons whose cell bodies are localized in the preoptic area and express NPFF receptors. These neurons extend axons to the pituitary gland, suggesting that they somehow enhance FSH gene expression in pituitary FSH-producing cells. FSH produced by this mechanism reaches the testes via the blood circulation and may be involved in the maintenance of testicular morphology and function.

This study was published in S. Tomihara et al, Proc Natl Acad Sci USA 119 (46) e2209353119 (2022).

*Former Assistant Professor, Department of Biological Sciences (at the time of the study)
Note 1) GnRH is an acronym for Gonadotropin-Releasing Hormone; GnRH neurons are neurons that make and release GnRH.
(Note 2) Peptide is a molecule consisting of multiple amino acids that acts as a hormone or a physiologically active substance in the brain. Peptides produced and released by neurons are called neuropeptides.

(Press release, November 8, 2022)

Published in the March 2023 issue of Faculty of Science News

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