In general, infertility is defined as not being able to get pregnant after one year of unprotected sex. Causes of infertility or reproductive problems include disease and aging, with male infertility just as common as female infertility. Many types of infertility result from disorders of pulsatile Gonadotropin-releasing hormone (GnRH) release, which is essential for reproduction. It is still unclear, however, as to what generates these hormonal pulses.
Now, researchers at the University of Otago have published the first direct evidence that it is kisspeptin neurons that generate the small, episodic hormone pulses that are crucial to normal reproductive functioning in humans and other mammals. The team state that their findings are another milestone in their world-leading efforts to understand the neural mechanisms underlying the brain’s master control of fertility.
Previous studies show that GnRH is a trophic peptide hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is synthesized and released from GnRH neurons within the hypothalamus. Episodic pulses of gonadotropin-releasing hormone (GnRH) to the pituitary gland are essential to maintain fertility. These episodic pulses, which occur roughly every hour or so, prompt the pituitary to release FSH and LH into the bloodstream also in a pulsatile manner. A very common cause of infertility in women, polycystic ovarian syndrome, is caused when pulses occur too fast. The team state that the key unresolved question has been what the underlying mechanism is that generates the GnRH pulses.
The current study used state-of-the-art optogenetic techniques to selectively activate kisspeptin neurons in a particular part of the brain’s hypothalamus in mice. After measuring blood samples the lab observed that activating this small population of kisspeptin neurons was remarkably potent at generating pulses of LH secretion. In contrast when the group activated the kisspeptin neurons in mice lacking kisspeptin receptors on their GnRH neurons, no LH pulses were generated.
The team surmise that their findings represent an important insight that will inform future efforts to develop new fertility treatments aimed at producing more or fewer GnRH pulses, depending on the problem.