Agents that increase phosphatidic acid inhibit the LH-induced testosterone production
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
Originalsprog | Engelsk |
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Tidsskrift | Molecular and Cellular Endocrinology |
Vol/bind | 104 |
Udgave nummer | 2 |
Sider (fra-til) | 229-235 |
Antal sider | 7 |
ISSN | 0303-7207 |
Status | Udgivet - 1 sep. 1994 |
ID: 45561843