Fresh insights into cells regulating puberty and reproduction

Gonadotrophs, cells in the pituitary gland involved in regulating puberty and reproduction, have a dual origin and are primarily produced after birth in mice, researchers have found.

Scientists at the Francis Crick Institute, London, aimed to understand how gonadotrophs are produced in mice by characterising stem cell differentiation in the pituitary gland (see BioNews 488). They found that gonadotrophs originate from two different populations, with the majority generated after birth, rather than in the embryo.

'Our discovery that gonadotrophs are mainly produced after birth is important as it highlights an opportunity to intervene, which would be difficult if they were mainly produced in the embryo,' said Daniel Sheridan, former PhD student at the Francis Crick Institute and first author of the study published in Nature Communications.

Gonadotrophs are specialised cells with a key role in reproduction. They first appear in the embryonic pituitary, a gland in the brain, home to various endocrine cells with roles in stress, growth and metabolism. Gonadotrophs produce the luteinising (LH) and follicle-stimulating (FSH) hormones responsible for promoting gamete (eggs or sperm) maturation.

The pituitary also contains a pool of stem cells with the ability to self-renew or differentiate into all endocrine cell types. After birth, there is a surge of activity in the pituitary called 'minipuberty' which happens both in mice and humans. In this study, researchers marked pituitary stem cells with fluorescent proteins to track and follow their differentiation from birth to puberty (see BioNews 231). Their results suggest that these stem cells mostly produce new gonadotrophs in both male and female mice.

Dr Karine Rizzoti, a principle laboratory research scientist at the Francis Crick Institute and co-senior author of the study, 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.'

Based on their developmental origin, embryonic and postnatal gonadotrophs take different locations in the gland. The dual origin and position could be linked with differences in their function or regulation. Moreover, the surge in production after birth in 'minipuberty' offers a 'window of opportunity' for diagnosis, or even treatment, of genetic disorders which can impact sexual development such as congenital hypogonadotropic hypogonadism (CHH).

Professor Robin Lovell-Badge, co-senior author, a principal group leader at the Francis Crick Institute, and chair of trustees at PET, 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.'

Researchers next plan to investigate what is stimulating the stem cells to become gonadotrophs specifically, after experiments in the lab suggested it might be the physiological context. 'We haven't yet found what stimulates the stem cells to become gonadotrophs, which would help us understand how to treat conditions affecting puberty,' said Sheridan.