Agents that increase phosphatidic acid inhibit the LH-induced testosterone production.
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 microM) induced an increased level of [3H]PtdOH in isolated rat Leydig cells, prelabeled with [3H]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 (4 beta-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.
Lauritzen
L
L
Department of Biological Sciences, Royal Danish School of Pharmacy, Copenhagen.
Nielsen
L L
LL
Vinggaard
A M
AM
Hansen
H S
HS
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology*; D008297:Male; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013110:Sphingosine / Q000494:pharmacology; D013739:Testosterone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D009227:Myristic Acids; D010712:Phosphatidic Acids; D019814:Myristic Acid; D000001:Calcimycin; D013739:Testosterone; D003994:Bucladesine; D007986:Luteinizing Hormone; D011433:Propranolol; D000242:Cyclic AMP; D002786:Cholesterol Side-Chain Cleavage Enzyme; D010739:Phospholipase D; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate