Researchers Identify Dual Origin of Cells Controlling Puberty and Reproduction

Researchers at the Francis Crick Institute have found that gonadotrophs, cells in the pituitary gland that regulate puberty and reproduction, arise from two distinct populations. Contrary to previous belief that these cells develop mainly in the embryo, most gonadotrophs are produced after birth.

The research is published in Nature Communications.

Gonadotroph development in the pituitary gland

The pituitary gland is a small organ located at the base of the brain. Gonadotrophs within this gland secrete hormones that stimulate the ovaries or testes to mature and produce eggs or sperm. These cells first appear during embryonic development and increase in number after birth.

Earlier research from the Crick had identified a population of stem cells specific to the pituitary gland. These stem cells can renew themselves or specialize into any hormonal cell type found in the gland. Their role was unclear, but the current study, published in Nature Communications, reveals that most gonadotrophs originate from these stem cells after birth.

Using genetic markers to trace the fate of these stem cells in mice from birth to one year old, the researchers observed that the stem cells almost exclusively became gonadotrophs rather than other pituitary cell types. This development occurred during a period known as ‘minipuberty’, between birth and puberty in mice.

The two gonadotroph populations were found in separate regions of the pituitary gland. Embryonic gonadotrophs remained in place throughout life, while those derived from stem cells spread across the gland after birth.

Investigating factors driving gonadotroph formation

The team explored what signals direct stem cells to become gonadotrophs. When isolated in the laboratory, the stem cells could develop into various pituitary cell types, suggesting the in vivo environment influences their fate.

Blocking gonadotrophin-releasing hormone (GnRH) led to smaller ovaries and testes but did not prevent stem cells from becoming gonadotrophs. This indicates GnRH is not the trigger for their production. Similarly, inhibiting sex hormones such as testosterone had no effect on gonadotroph development.

These results suggest that physiological changes associated with birth, such as leaving the maternal environment, may provide the signal for stem cells to produce gonadotrophs at the appropriate time.

Minipuberty as a critical period

Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder in which individuals do not produce GnRH. This results in gonadotrophs failing to produce hormones necessary for puberty, causing delayed or incomplete sexual development.

Humans, like mice, experience minipuberty, a surge of pituitary activity shortly after birth lasting several months to years. The researchers propose that humans may also have two gonadotroph populations, with most cells generated during minipuberty.

This finding suggests that early life represents a key window to diagnose and potentially treat disorders such as CHH by monitoring gonadotroph development.

Karine Rizzoti, Principal Laboratory Research Scientist in the Stem Cell Biology and Developmental Genetics Laboratory at the Crick and co-senior author, said: “We’ve known about this population of stem cells in the pituitary for a while, but it took the right tools used at the right time to see just how important they are. Instead of the previously held idea that gonadotrophs all have the same origin, we instead found that there are two waves of generation, before and after birth.”  

Robin Lovell-Badge, Principal Group Leader of the Stem Cell Biology and Developmental Genetics Laboratory at the Crick and co-senior author, said: “Now that we know there are two discrete populations of gonadotrophs, we can start to unpick which group is affected during disorders like CHH that cause delayed or absent puberty. The next step is to look at the role of each population in mice with similar disorders in puberty.”

Reference: Sheridan D, Chakravarty P, Golan G, et al. Gonadotrophs have a dual origin, with most derived from early postnatal pituitary stem cells. Nat Commun. 2025;16(1):4280. doi: 10.1038/s41467-025-59495-7

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