TY - JOUR
T1 - Agents that increase phosphatidic acid inhibit the LH-induced testosterone production
AU - Lauritzen, L.
AU - Nielsen, L.-L.A.
AU - Vinggaard, Anne Marie
AU - Hansen, Harald S.
PY - 1994/9/1
Y1 - 1994/9/1
N2 - The results of the present study point to phosphatidic acid (PtdOH) as a possible intracellular messenger, which might be involved in local modulation of testicular testosterone production in vivo. Propranolol (27-266 µM) induced an increased level of [H]PtdOH in isolated rat Leydig cells, prelabeled with [H]myristate, and at the same time a strong dose-dependent inhibition of the acute testosterone production stimulated by luteinizing hormone (LH). The inhibition was not bypassed by the addition of dibutyryl-cAMP but was overcome, when 22(R)-hydroxycholesterol was added as a direct substrate for cytochrome P-450 side chain cleavage enzyme. Thus, the inhibition appears to be exerted at a point distal to cAMP-generation but before the first enzyme in the testosterone synthetic pathway. Treatment with other agents (4ß-phorbol 12-myristate 13-acetate (PMA), A23187, and sphingosine) giving rise to increases in the PtdOH-level resulted in the inhibition of the LH-induced testosterone formation as well, thus indicating a connection between the two effects. Furthermore, we were able to demonstrate a highly significant correlation between the PtdOH-increase and the inhibition of the LH-stimulated testosterone production. This may suggest a causal relationship between these two parameters.
AB - The results of the present study point to phosphatidic acid (PtdOH) as a possible intracellular messenger, which might be involved in local modulation of testicular testosterone production in vivo. Propranolol (27-266 µM) induced an increased level of [H]PtdOH in isolated rat Leydig cells, prelabeled with [H]myristate, and at the same time a strong dose-dependent inhibition of the acute testosterone production stimulated by luteinizing hormone (LH). The inhibition was not bypassed by the addition of dibutyryl-cAMP but was overcome, when 22(R)-hydroxycholesterol was added as a direct substrate for cytochrome P-450 side chain cleavage enzyme. Thus, the inhibition appears to be exerted at a point distal to cAMP-generation but before the first enzyme in the testosterone synthetic pathway. Treatment with other agents (4ß-phorbol 12-myristate 13-acetate (PMA), A23187, and sphingosine) giving rise to increases in the PtdOH-level resulted in the inhibition of the LH-induced testosterone formation as well, thus indicating a connection between the two effects. Furthermore, we were able to demonstrate a highly significant correlation between the PtdOH-increase and the inhibition of the LH-stimulated testosterone production. This may suggest a causal relationship between these two parameters.
UR - http://www.scopus.com/inward/record.url?scp=0028144761&partnerID=8YFLogxK
M3 - Journal article
AN - SCOPUS:0028144761
SN - 0303-7207
VL - 104
SP - 229
EP - 235
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 2
ER -