In various animals, such as some fish, early exposure during development to environmental stressors, including high temperature, causes genetically female animals to develop male gonads. Although the process of sex reversal has been studied at a molecular level during gonad development, the role of the brain remains enigmatic. Now, Juan Fernandino and colleagues provide the first evidence that the central nervous system regulates environmental masculinisation in the medaka. They show that corticotropin-releasing hormone B (crhb) is upregulated in embryos incubated at high temperature during the period of gonadal sex determination. Using CRISPR/Cas9 to mutate the two genes encoding receptors for Crh, the authors show that mutating both crhr1 and crhr2 reduces female-to-male sex reversal at high temperatures. The process of masculinisation in these mutants can be rescued through the addition of cortisol, which acts downstream of Crh. Together, these data indicate that the hypothalamic-pituitary-interrenal axis is functional during the period of gonadal fate specification and contributes to environmental sex determination. This work challenges previous assumptions that sexual fate begins in the gonad, and reveals an important mechanism for sex reversal in response to increased temperatures.
Corticotropin-releasing hormone takes the heat off sex reversal Free
Corticotropin-releasing hormone takes the heat off sex reversal. Development 15 April 2019; 146 (8): e0803. doi:
Download citation file:
Advertisement
Cited by
Save the date - Human Development: Stem Cells, Models, Embryos

We will be hosting a 2026 Human Development: Stem Cells, Models, Embryos meeting. We have teamed up with the Wellcome-funded consortium, the Human Developmental Biology Initiative (HDBI) to co-organise this event, which will bring together researchers from around the world, united by an interest in understanding human developmental biology. Save the date for 7-9 September 2026 and register.
Development presents…

Development is delighted to host a webinar series showcasing the latest developmental biology and stem cell research. The webinars are held each month with talks from postdocs applying for independent positions as part of our Pathway to Independence programme. Visit Development presents... on the Node to see which stimulating topics are coming up in the next few months.
Meet our 2025 Pathway to Independence (PI) fellows

We are delighted to announce our third cohort of PI fellows - researchers whom we will be supporting as they transition from postdoc to Principal Investigator. Read about the eight talented fellows chosen, whom we're excited to be working with as they navigate the job market.
From bench to business

In this Perspective, researchers who have transitioned from academia to industry tell us how they have navigated patents, intellectual property, investors and biotechnology start-ups to bring new biological advances from the bench and into the boardroom.
Browse by subject
![Development logo - Browse by subject: Explore Development's content, now easily accessible by subject area. The ad has a black background with three vibrant scientific images: a developing embryo on the left, a green plant-like structure in the center, and a gastruloid (a circular cell with a bright pink center and blue outer ring) on the right. [Blue button: browse content].](https://cob.silverchair-cdn.com/ImageLibrary/Development/Snippets/2025_05_Dev_Browse-by-subject_600x230_Snippet.png?versionId=9135)
From cardiovascular development and regeneration to tissue engineering and organoids, Development’s browse by subject archive allows you to access the latest papers (from late 2024 onwards) on a particular field of interest. In addition to our curated subject collections, these subject pages allow readers to browse a broader range of papers organised by topic.