Submitted by Emily Rigby on Wed, 22/10/2025 - 11:09
In mammals, fertility is controlled by the brain via the Hypothalamic-Pituitary-Gonadal (HPG) axis. Before puberty, HPG hormone secretion is suppressed or low. Just before puberty, sex steroid hormones released from the gonads increase and act on the hypothalamus and pituitary. What regulates the activation of the HPG axis at puberty, and controls fertility in adults? Seminal work from Professor Bill Colledge and others ~20 years ago showed that kisspeptin-releasing (Kiss1) neurons in the hypothalamus are needed for puberty and fertility (Seminara et al, 2003). Puberty represents a critical period of mammalian development and in other brain regions, development is associated with neuronal plasticity.
A new study led by Dr Sue Jones in collaboration with Professor Colledge has revealed estrogen-dependent neuronal plasticity occurring in Kiss1 neurons in female mice, beginning just before the onset of puberty. In collaboration with Dr Erik Hrabovsky’s Lab from the Hungarian Research Network, we identified corresponding changes in specific ion channel genes that could account for the changes in neuronal activity. This plasticity leads to neuronal activity that could support the pulsatile release of HPG hormones in fertility, and so these changes at puberty could represent the maturation of ARC Kiss1 neurons in preparation for fertility.
All of the work in Cambridge was carried out by former PhD student (now a postdoc at LMB), Dr Yuanxin Zhang and current PhD student, Leonie Pakulat, with Part II student Lauren Campbell contributing to data analysis.
Read the article Neuronal plasticity at puberty in mouse hypothalamic Kiss1 neurons that control fertility at https://www.pnas.org/doi/10.1073/pnas.2512855122