The physiological interactions of reproductive hormones in humans
Research type
Research Study
Full title
The physiological interactions of reproductive hormones in humans
IRAS ID
151586
Contact name
Waljit S Dhillo
Contact email
Sponsor organisation
Joint research complicance office, Imperial College London and Imperial College NHS Trust
Research summary
Summary of Research
Infertility affects 1 in 7 couples in the UK. Unfortunately, some cannot be treated leaving affected couples with devastating psychological and social consequences. Puberty and fertility are regulated by production of gonadotrophin releasing hormone (GnRH) from a small part of the brain called the hypothalamus, which stimulates the release of gonadotrophins (LH, FSH) in a pulsatile manner into the bloodstream.Over the last decade, it has been found that two hormones, kisspeptin and neurokinin-B (NKB) play a critical role in regulating GnRH release at the time of puberty, pregnancy and infertility in both men and women. In animal models it has been shown that those same nerve cells in the hypothalamus express the receptors for kisspeptin and NKB as well as dynorphin, which is an opioid. As such these nerve cells are termed KNDy neurones (kisspeptin/NKB/dynorphin), and are yet to be investigated in humans.
Our previous ethics-approved studies suggest that an injection of kisspeptin or NKB safely stimulates the release of gonadotrophins in healthy men and women, and is well tolerated. Others have suggested that naltrexone (an opioid antagonist), when given orally or by injection as a surrogate of dynorphin, also safely increases gonadotrophin release and is well tolerated. Furthermore oral opioid receptor antagonists have long been described as a reliable endocrine test of pituitary function, and are widely used in clinical practice.
We therefore aim to study these KNDy neurones by determining the physiological interactions of these three hormones on stimulating reproductive hormone release. In doing so we will greatly advance understanding of human reproductive physiology, and may identify future treatments for infertility.
Summary of Results
Co-administration of kisspeptin and an agent that acts on the opioid receptor enhanced reproductive hormone release in healthy men.REC name
London - Central Research Ethics Committee
REC reference
14/LO/1098
Date of REC Opinion
28 Jul 2014
REC opinion
Further Information Favourable Opinion