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Activation of Kiss1 neurons in the preoptic hypothalamus stimulates testosterone synthesis in adult male mice

ABSTRACT: Kisspeptin-expressing neurons in the rostral periventricular region of the third ventricle (RP3V) play an essential role in female reproduction. However, adult male mice were reported to have very few Kisspeptin-expressing neurons in the RP3V compared to females. This led to the hypothesis that Kiss1 RP3V neurons are responsible for the ability of females, but not males, to generate a surge of LH, triggering ovulation and steroid synthesis in the female. Using mouse genetics and cell type-specific gene expression analysis, we show that male mice harbor almost as many Kiss1 RP3V neurons as the female and that gene expression in these neurons is very similar. Specific activation of male Kiss1 RP3V neurons expressing viral-encoded hM3Dq caused a surge in serum testosterone levels. These results demonstrate that Kiss1 RP3V neurons are present in the adult male and fully capable of regulating the hypothalamic/pituitary/gonadal axis. We suggest that these neurons may continue to play a role in reproductive behavior in adult male mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE165015 | GEO | 2021/06/01

REPOSITORIES: GEO

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Project description:Adult reproductive behaviors in Drosophila melanogaster males and females are vastly different. Yet, neurons that express sex-specifically spliced fruitless transcripts (fru P1) underlie these behaviors in both sexes. How the same set of neurons can drive such different behaviors is an important and unresolved question in developmental genetics. A particular challenge is that fru P1-expressing neurons are only 2-5% of the adult nervous system, making studies of adult head tissue, or even the whole brain, unlikely to yield informative inferences. Translating Ribosome Affinity Purification (TRAP) identifies the actively translated pool of mRNAs from fru P1-expressing neurons and allowed us to conduct a sensitive, cell-specific assay of gene expression. The male and female fru P1-expressing neurons have a shared set of 1,642 genes with enriched TRAP transcripts that form a distinct repertoire, relative to TRAP analyses of all neurons in the adult head. Further, there are a striking number of genes (3,147) that have sex-biased TRAP enrichment in fru P1-expressing neurons. Yet, most of these genes (3,107) have only male-biased TRAP enrichment. This suggests an underlying mechanism to generate dimorphism in behavior, with the transcript repertoire that specifies female behaviors present in both sexes and a large additional set of genes with expression in the male dramatically altering the pattern. Thus, these additional genes invoke the male-specific behaviors by establishing cell fate in the same context of gene expression observed in females. These results suggest a possible global mechanism for how distinct behaviors can arise in different environments, from a shared set of neurons. Libraries were prepared from five independent biological replicates, from TRAP adult heads samples from males and females, and the mRNA input from adult heads from males and females. For each experimental condition, approximately 1,000 flies that were 8 to 24 hours post-eclosion were used.

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Activation of Kiss1 neurons in the preoptic hypothalamus stimulates testosterone synthesis in adult male mice

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