Posted by: Maria/MD Health Forum.com Team

It’s quite funny how people see things differently. Try to ask their opinion about something very simple, and I bet that you will get varied responses. Like how did famous writers define kiss? According to Edward Estlin Cummings, kisses are a better fate than wisdom. Oscar Wilde’s view was rather different, because to him, a kiss is something that can ruin a human life. Experts in the field of reproductive science, however, have unanimous view on KiSS, they consider it as a remarkable discovery. However, it’s not the smack-on-the-lips-thing that the general public knows, but rather a gene that was discovered by researchers at the Pennsylvania State College of Medicine years ago.

Kiss-1 gene was first named metastin because it was thought to have a role in tumor metastasis, but its discoverers decided to associate the gene with their town’s renown product: the Hershey chocolate kiss, the letters SS which stand for Suppressor Sequence are incorporated to the gene’s name. Kisspeptin hormone is a product of the KiSS-1 gene. A few years after its discovery, researchers identified the role of kisspeptin and its receptor GPR54 in reproduction. From then on, the discovery of kisspeptin has been considered as the greatest advance in reproductive science in since the 1970’s- the time when the Gonadotropin releasing hormone was discovered.

The GPR54 which is a G protein-linked receptor was first identified in 1999. A receptor needs a ligand that will bind to it in order to trigger a cellular response, it basically works like a lock and key. A ligand can be in a form of peptide, a hormone, toxin or drugs. Kisspeptin, the natural ligand for GPR54 was discovered in 2001. Kisspeptin and GPR54 are expressed most notably in the brain, placenta and pancreas. In 2003, two independent groups of scientists reported that mutations in GPR54, would result to the absence of puberty and infertility in humans. In the same year, one group studied a GPR54 knockout (genetically engineered) mouse and found out that GPR54 mutation caused sterility and an absence of puberty. All these studies strongly suggested that kisspeptin-GPR54 signaling was crucial for puberty. Since then, many scientists focused on unraveling kisspeptin’s mechanism of action, they have also been finding ways of using it for new therapies for infertility, contraception and precocious and delayed puberty.

Puberty in a nutshell
Puberty takes place once the gonadotropin-releasing hormone (GnRH) is secreted, this initiates a chain reaction of chemical messages. In the hypothalamus GnRH are secreted by the nerve cells in a constant fashion. Each secretion stimulates the pituitary gland to secrete follicle-stimulating hormone (FSH) and lutenizing hormone (LH) straight off into the circulation. Increasing levels of LH and FSH will then cause the reproductive glands: ovaries and testes, to produce the estradiol and testosterone, the sex hormones responsible for the physical and emotional changes that one has to live with as he or she goes through this thing called puberty.

KiSS sets off puberty
On January 2005, the researchers at the University of Pittsburg reported that they have significant evidence that the kisspeptin molecule and the GPR54 gene are the key to the commencement of puberty when the gonadotropin-releasing hormone is released. The group found out that GPR54 and KiSS-1 are expressed inside the hypothalamus of primates during puberty. Additionally, the researchers discovered that by administering kisspeptin to the animals, they could reactivate the reproductive hormones from their childhood hibernation. When kisspeptin was given to male monkeys, their LH levels increased within 30 minutes, the levels were 25 times more that the baseline which was at zero.

KiSS for Fertility
A new research suggests that hormone kisspeptin shows potential as new therapy for infertlity. This study was led by Waljit Dhillo Department of Investigative Medicine at Imperial College London. Researchers reported that giving kisspeptin to women with infertility can activate the release of sex hormones which control the menstrual cycle. In this study, a group of ten women who were not menstruating and were infertile were injected with either kisspeptin (n=5) or saline (control, n=5).  Blood samples were then taken to measure their levels of luteinising hormone (LH) and follicle stimulating hormone (FSH) which are two sex hormones responsible for ovulation and fertility.  The women who were given Kisspeptin led to a 48-fold increase in LH and 16-fold increase in FSH, when compared to the control group. This is the only study to date that shows kisspeptin’s ability to stimulate sex hormones in infertile women.

According to Dr Dhillo, their findings suggest that kisspeptin therapy can benefit women who have low sex hormone levels because administering kisspeptin could restore reproductive functions. They plan to focus their future studies on determining the best protocol for repeated kisspeptin administration with the goal of developing a new treatment for infertility.

So what’s in a ‘KiSS’? For young ones, the product derived from kiSS1 turns puberty switch on, but for more that 70 million couples affected by infertility worldwide, it offers promise.

References:
http://www.chronicle.pitt.edu/media/pcc050207/sci1_first_kiss.html accessed 23.3.09

Society for Endocrinology (2009, March 19). Hormone Offers Promise As Fertility Treatment.

Infertility and the provision of infertility medical services in developing countries
Willem Ombelet1,6, Ian Cooke2, Silke Dyer3, Gamal Serour4 and Paul Devroey5

Photo credit: Manuel Andres

Tags: GPR54, infertility, KiSS1, Kisspeptin, puberty

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