Phospholipase C-eta enzymes as putative protein kinase C and Ca2+ signalling components in neuronal and neuroendocrine tissues

Phosphoinositol-specific phospholipase C enzymes (PLCs) are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C activation. A sixth class of phosphoinositol-specific PLC with a novel domain structure, PLC-eta (PLCeta) has recently been discovered in mammals. Recent research, reviewed here, shows that this class consists of two enzymes, PLCeta1 and PLCeta2. Both enzymes hydrolyze phosphatidylinositol 4,5-bisphosphate and are more sensitive to Ca2+ than other PLC isozymes and are likely to mediate G-protein-coupled receptor (GPCR) signalling pathways. Both enzymes are expressed in neuron-enriched regions, being abundant in the brain. We demonstrate that they are also expressed in neuroendocrine cell lines. PLCeta enzymes therefore represent novel proteins influencing intracellular Ca2+ dynamics and protein kinase C activation in the brain and neuroendocrine systems as putative mediation of GPCR regulation

Dissociated effect of buserelin on luteinizing hormone (LH) and alpha subunit in men

Chronic treatment with LHRH analogs is known to depress testosterone (T) values to castration levels. In contrast to results from animal experiments, studies in humans indicate that a pituitary-dependent mechanism predominates in the suppression of plasma T. However, this reduction in T levels may occur when LH values are within or below the normal range. One explanation for this result has been that while absolute values of LH in serum may not change, the bioactivity of LH is reduced. The present study has been performed to determine whether this discrepancy between LH and T values is obscured by the hypersecretion of the alpha-subunit which is devoid of any biological activity but crossreacts in most RIAs with LH. Following 2 days of blood collection to establish basal serum hormone levels, six men with prostatic cancer were treated with the LHRH agonist, Buserelin (500 micrograms sc, daily injection) for 15 days. The most significant endocrine responses at the end of this treatment were as follows: 1) T levels were depressed to the castration range; 2) no change was seen in the LH values with a conventional RIA procedure which crossreacted with the alpha-subunit; 3) a significant decrease was found in the LH values evaluated with an immunoradiometric (IRMA) method, which shows no cross-reactivity with the alpha-subunit; 4) there was a significant increase in the alpha-subunit levels; and 5) serum FSH levels were significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS