We are delighted that Isabel Huang Doran has been awarded a prestigious Wellcome Career Development Fellowship.
Reproductive problems are more common in individuals who are overweight or obese. For example, children with weight problems are more likely to experience early puberty and mature before lean children. In adulthood, women are at higher risk of heavy or irregular periods, fertility problems and cancer of the womb, whilst men are prone to low hormone levels. As a result, many patients experience significant symptoms day-to-day, with adverse consequences on their quality of life. Unfortunately, the link between weight and reproductive function is not well understood, and treatment options are currently limited.
Reproductive function is tightly orchestrated by a series of hormones: hormones made in the brain (in a pea-sized gland called the pituitary gland) communicate with reproductive organs (ovaries in women, testes in men), which in turn produce sex hormones (estrogen and testosterone). Collectively, these hormones control different aspects of reproductive function, including menstruation in women, and production of eggs and sperm. Even slight disruption of these hormones can lead to symptoms.
The “master regulator” of reproductive hormones is located in the brain, in a region known as the hypothalamus. This becomes activated shortly before puberty, kickstarting the release of pituitary hormones, which in turn activates the ovaries and testes. A neighbouring region of the hypothalamus regulates appetite and body weight, and we already know that these two control centres interact. For example, in previous work led by Professor Farooqi, we learned that the hormone leptin, released from fat cells, is essential for regulating food intake by acting on the hypothalamus. Leptin is also essential for reproductive function, and without it children do not enter puberty.
In her fellowship, Isabel will investigate other molecular players in the hypothalamus that link body weight to reproductive function. Specifically, she will study new genes in children with both severe, early-onset obesity and early puberty. By investigating the function of these genes in the hypothalamus, we hope to uncover new mechanisms linking weight and reproduction function. In doing so, we aim to provide new insights to help clinicians manage reproductive disorders in men, women and children with weight problems.