News | Major discovery: pituitary gonadotrophs arise during two distinct developmental periods
A study from the Francis Crick Institute in the UK has transformed understanding of the developmental origins of gonadotrophs. The team confirmed that these pituitary cells, which regulate puberty and reproductive function, do not arise entirely during embryonic development as previously thought. Most come from a second developmental wave after birth during a key stage called minipuberty.
Gonadotrophs are located in the small but essential pituitary gland at the center of the brain. Their hormones stimulate the ovaries or testes to mature and initiate egg or sperm production. Scientists long believed that these cells formed mainly during embryonic development, but this study challenges that view.
Postnatal stem cells do most of the work
The Crick team previously identified tissue-specific stem cells in the pituitary that can self-renew and differentiate into several pituitary cell types. Their role in the living body, however, remained unclear.
In this study, published in Nature Communications, scientists used genetic labeling to track these stem cells in mice. From birth to one year of age, the cells differentiated almost exclusively into gonadotrophs rather than other pituitary cells. This process began shortly after birth and continued until before puberty, during minipuberty in mice.
The study also found that embryonic and postnatal gonadotrophs occupy different pituitary regions. Embryonic cells remain in place throughout life, while postnatal cells gradually spread across several regions, indicating different functions and fates.
What activates these stem cells?
If the gonadotrophs are not generated during embryonic development, what signals stem cells to become them after birth? The team tested several hormonal interventions:
First, they blocked gonadotropin-releasing hormone (GnRH), a brain hormone that activates gonadotroph function. Although the testes and ovaries became smaller, stem cells still differentiated normally into gonadotrophs, showing that GnRH is not the key trigger.
Blocking sex hormones such as testosterone or removing the gonads also had no clear effect. The team therefore suggested that physiological changes after separation from the mother—possibly birth itself—may trigger this change in cell fate.
Minipuberty: a new window for intervention
The discovery has implications for basic science and may change clinical intervention for disorders of pubertal development.
People with congenital hypogonadotropic hypogonadism (CHH), for example, cannot secrete GnRH, so gonadotrophs are not activated and puberty is delayed or absent. Like mice, humans experience minipuberty after birth, a brief period when the pituitary is activated and development begins.
The researchers believe humans may also have two gonadotroph populations: one produced during embryonic development and another derived from stem cells after birth. If confirmed, clinicians may be able to assess stem-cell production soon after birth, predict pubertal disorders, and intervene before normal pubertal development is missed.
Expert comments: a major shift in understanding
“We have long known that these stem cells exist in the pituitary, but we could not identify their true function. We finally used the right tools at the right time to reveal their major role.”
—Dr. Karine Rizzoti, principal research scientist, Stem Cell Biology and Developmental Genetics Laboratory, Crick Institute
“Our study shows that gonadotrophs are not all produced at once during embryonic development, meaning clinical intervention may be possible at more flexible times.”
—Dr. Daniel Sheridan, former Crick Institute doctoral student and first author
“Now that we know gonadotrophs have two distinct origins, we can investigate which population is affected in conditions such as CHH.”
—Professor Robin Lovell-Badge, senior group leader, Stem Cell Biology and Developmental Genetics Laboratory, Crick Institute
News | Major discovery: pituitary gonadotrophs arise during two distinct developmental periods
News | Major discovery: pituitary gonadotrophs arise during two distinct developmental periods
A study from the Francis Crick Institute in the UK has transformed understanding of the developmental origins of gonadotrophs. The team confirmed that these pituitary cells, which regulate puberty and reproductive function, do not arise entirely during embryonic development as previously thought. Most come from a second developmental wave after birth during a key stage called minipuberty.
Gonadotrophs are located in the small but essential pituitary gland at the center of the brain. Their hormones stimulate the ovaries or testes to mature and initiate egg or sperm production. Scientists long believed that these cells formed mainly during embryonic development, but this study challenges that view.
Postnatal stem cells do most of the work
The Crick team previously identified tissue-specific stem cells in the pituitary that can self-renew and differentiate into several pituitary cell types. Their role in the living body, however, remained unclear.
In this study, published in Nature Communications, scientists used genetic labeling to track these stem cells in mice. From birth to one year of age, the cells differentiated almost exclusively into gonadotrophs rather than other pituitary cells. This process began shortly after birth and continued until before puberty, during minipuberty in mice.
The study also found that embryonic and postnatal gonadotrophs occupy different pituitary regions. Embryonic cells remain in place throughout life, while postnatal cells gradually spread across several regions, indicating different functions and fates.
What activates these stem cells?
If the gonadotrophs are not generated during embryonic development, what signals stem cells to become them after birth? The team tested several hormonal interventions:
First, they blocked gonadotropin-releasing hormone (GnRH), a brain hormone that activates gonadotroph function. Although the testes and ovaries became smaller, stem cells still differentiated normally into gonadotrophs, showing that GnRH is not the key trigger.
Blocking sex hormones such as testosterone or removing the gonads also had no clear effect. The team therefore suggested that physiological changes after separation from the mother—possibly birth itself—may trigger this change in cell fate.
Minipuberty: a new window for intervention
The discovery has implications for basic science and may change clinical intervention for disorders of pubertal development.
People with congenital hypogonadotropic hypogonadism (CHH), for example, cannot secrete GnRH, so gonadotrophs are not activated and puberty is delayed or absent. Like mice, humans experience minipuberty after birth, a brief period when the pituitary is activated and development begins.
The researchers believe humans may also have two gonadotroph populations: one produced during embryonic development and another derived from stem cells after birth. If confirmed, clinicians may be able to assess stem-cell production soon after birth, predict pubertal disorders, and intervene before normal pubertal development is missed.
Expert comments: a major shift in understanding
“We have long known that these stem cells exist in the pituitary, but we could not identify their true function. We finally used the right tools at the right time to reveal their major role.”
—Dr. Karine Rizzoti, principal research scientist, Stem Cell Biology and Developmental Genetics Laboratory, Crick Institute
“Our study shows that gonadotrophs are not all produced at once during embryonic development, meaning clinical intervention may be possible at more flexible times.”
—Dr. Daniel Sheridan, former Crick Institute doctoral student and first author
“Now that we know gonadotrophs have two distinct origins, we can investigate which population is affected in conditions such as CHH.”
—Professor Robin Lovell-Badge, senior group leader, Stem Cell Biology and Developmental Genetics Laboratory, Crick Institute
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