Disruption of GPR54 signaling

Was reading a book namely Epigenetics, how environment shapes our genes and in this book it talks about how frequent steroid users become desensitised to Testosterone over a period of time causing down regulation of the receptors and that they would eventually have to go further up the stream and administer GTRH to have any affect. One of the important points made was that GTRH neurons in the brain are responsible for testosterone production. Following this up: Failure of GnRH neurons to form the proper connections, or failure to successfully stimulate the pituitary with GnRH, means that puberty is not initiated. These disruptions to the GnRH system cause reproductive disorders like hypogonadotropic hypogonadism or [Kallmann Syndrome].

However, for kisspeptin to be involved in the regulation of GnRH release, it must also be sensitive to circulating sex steroid levels, as it is established that steroids produced by the gonads exert regulatory effects on FSH and LH levels through GnRH mediation. Thus, there are at least two possible scenarios: that either kisspeptin neurons express sex steroid receptors themselves, or they receive input about circulating sex steroid levels from a different mechanism .

Coexpression imaging of KISS1 mRNA (using vector red) and steroid receptors determined that neurons that express KISS1 mRNA are targets for the action of sex steroids in both male and female mice.