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Difference in testosterone sensitivity in male spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY)
K Magnusson1, A Wall, B J Meyerson
1Department of Medical Pharmacology, Uppsala University, Sweden.
Abstract:
The effects of castration and testosterone substitution on copulatory behavior and arginine-vasopressin (AVP) concentrations in the lateral septum (LS) were compared in the male spontaneously hypertensive rat (SHR) and its normotensive counterpart, the Wistar-Kyoto rat (WKY). The copulatory behavior was attenuated in the intact SHR and remained for a shorter time after castration than in the WKY males. A higher dose (1 mg/kg) of testosterone propionate (TP) was required in the castrated SHR to reestablish the copulatory behavior compared to the WKY (0.5 mg/kg). Following castration the main decline of AVP concentrations occurred over a period of 28 days. On postcastrational day 14, a time when approximately 50% of the initial AVP concentration remained, the decrease in the LS AVP content of the SHR surpassed that of the WKY. A dose-dependent increase of the AVP concentrations was achieved after 3 weeks of TP treatment (0.5 and 1.0 mg/kg, SC), which commenced 28 and 56 days after castration. The increase of AVP concentrations in the LS after a submaximal dose of TP (0.5 mg/kg) was less in the SHR than in the WKY. It is concluded that the gonadal hormone control of the copulatory behavior and AVP content in the terminal fields of the LS is characterised by a lower sensitivity in the SHR compared to the WKY. The data suggest that the low responsiveness to testosterone in the SHR comprises hypothalamic as well as extrahypothalamic neurons.