Brain injection of an androgen synthesis inhibitor rapidly affects recovery from anesthesia and androgen levels in males


Meeting Abstract

P1.32  Wednesday, Jan. 4  Brain injection of an androgen synthesis inhibitor rapidly affects recovery from anesthesia and androgen levels in males PRADHAN, DS*; SOLOMON-LANE, TK; WILLIS, MC; NAUDE, PW; GROBER, MS; Georgia State Univ., Atlanta; Georgia State Univ., Atlanta; Georgia State Univ., Atlanta; Univ. of Georgia, Athens; Georgia State Univ., Atlanta dpradhan1@student.gsu.edu

In many fishes, 11-Ketotestosterone (KT) activates male breeding phenotype. Bluebanded gobies are fish in which brain KT levels are several fold higher than the gonads. Synthesis of KT occurs via the sequential action of 11β-hydroxylase (converts testosterone to 11-Hydroxytestosterone, 11-OHT) and 11β-hydroxysteroid dehydrogenase (11β-HSD, converts 11-OHT to KT). In males, systemic implants of carbenoxolone (CBX), a specific 11β-HSD inhibitor that does not cross the blood brain barrier, decreases KT levels by 48% one day after treatment. These effects are gone in 4 d, suggesting that KT inhibition in testis may be compensated by KT synthesis from the brain. To test whether local changes in brain KT synthesis affect systemic changes, we intracerebroventricularly (icv) injected males (N=24) with three doses of CBX or vehicle. To establish basal physiological effects of CBX, we measured parameters of recovery from anesthesia. Males treated with the medium (24.7 mg/mL) and high (49.4 mg/mL) CBX doses took significantly longer to initiate ventilation and regain equilibrium compared to low doses (4.94 mg/mL) and controls (0 mg/mL). Medium and high doses also increased respiration in the first 5 min following initiation of ventilation. There was no effect of CBX on brain KT levels after 1 h. In contrast, systemic KT was decreased by the medium and high dose (75 % and 90 % respectively), and there was no effect of the low dose. The absence of local CBX effect suggests that the brain recovers rapidly from the inhibition of 11β-HSD. Systemic effects of CBX suggest there may be a lag between effects in the brain and KT accumulation in water.

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