Possible Interaction: Copper and Gonadotropin-Releasing Hormone

“Both increased androgen levels and copper accumulation in the hypophysis could be responsible for the blunted GnRH response.”

“Furthermore, … copper can interact with key …-pituitary-gonadal axis, notably gonadotropin-releasing hormone (GnRH) and neurokinin B. Interestingly, recent phylogenetic analysis of the sequences of GnRH-related peptides indicates that copper … ancient property of this neuropeptide family, which has been variously retained, modified or lost in the different taxa.”

“Our studies have shown that complexes of copper (Cu²+) with gonadotropin-releasing hormone (GnRH) are even more effective in the release of LH than native GnRH.”

“Complex of copper with the gonadotropin-releasing hormone, GnRH , competed more efficiently for the GnRH receptor than native GVRH, while complexes of nickel with GnRH and zinc with GnRH had slightly lower affinity.”

“Moreover, exposure to Cu and PGE2 results in an amplified release of LHRH which is partially Ca2+ dependent, thus, resembling the release process stimulated by PGE2 alone.”

“ Copper , complexed to histidine (CuHis), stimulates LHRH release from explants of the median eminence area (MEA).”

“When incubation was carried out … of a nonsaturating concentration of copper (50 microM), the fractional amount (… total MEA content) of LHRH released from the MEA of castrated rats was significantly (p less than 0.001) … that from sham-operated rats; stimulated release being 0.9% and 1.4%, respectively.”

“ Copper led to a transient increase in the rate of LHRH release; the maximal rate was attained 15 min after transfer of the MEA to copper-free medium.”

“Furthermore, this DTT-inhibitable … summary the findings that copper, … LHRH release and that the apparent Km of 4 microM for copper in this process is within the concentration range for … rapidly with the LHRH granule in an energy-requiring fashion and that, consequent to this interaction, LHRH release occurs.”

“We propose that copper may affect LHRH release as follows: copper, bound to an intracellular chelator (protein, peptide, or amino acid), oxidizes thiols of the LHRH granule, leading to a change in granule‐membrane permeability and hence to LHRH release.”