| Abstrakt: |
The efficacy of cutaneously applied luteinizing hormone releasing hormone (LH-RH) in stimulating LH release in the chronically ovariectomized, estrogen/progesterone-blocked rat and ovulation in the chlorpromazine-blocked, proestrous rat was investigated. Following the cutaneous application of 25 or 100 mug of LH-RH in 100% dimethyl sulfoxide (DMSO), serum LH rose to a peak at 1 hr, then declined toward basal levels in the ensuing 3 to 4 hr. LH-RH applied cutaneously in either 100% DMSO or 0.9% NaCl was also capable of inducing ovulation in the chlorpromazine-blocked, proestrous rat; however, LH-RH in 0.9% NaCl did not yield a linear log-dose-response relationship, therefore a valid ED50 potency ratio for DMSO/0.9% NaCl could not be estimated. Nonetheless, 0.9% NaCl was a considerably less effective cutaneous vehicle than DMSO. Cutaneous application of LH-RH in DMSO in doses of 100, 50, 25, 10, 5, 2.5 and 1 mug induced ovulation in 100%, 100%, 90%, 73%, 30%, 10% and 0% of the rats, respectively. When the percent ovulation response was transformed to probits and plotted against the logarithm of the LH-RH dose an approximately linear log dose-response was obtained; the same relationship also held true for ovulation induction following sc LH-RH administration. In turn, the ED50's of these two parallel dose-response curves yielded a potency ratio estimate (sc/cutaneous) of 0.025, suggesting that 2.5% of the cutaneously applied LH-RH dose was absorbed through the skin in a biologically active form. These data indicate that DMSO privdes a convenient cutaneous vehicle for the administration of LH-RH. |
