Testosterone (T) secreted in short pulses several times each day is essential for the maintenance of male sex behavior (MSB) in mammals. Blood T concentrations are relatively low during inter-pulse intervals. Assessment of androgenic influences on MSB of rodents has, with very few exceptions, involved either injections of pure or esterified hormones dissolved in oil or implantation of constant release capsules that generate supraphysiological and/or constantly elevated T concentrations. The minimum daily concentration of T necessary to maintain and restore MSB when T is delivered as a discrete short pulse remains unspecified; nor is it known whether infrequent T pulses in the physiological range sustain MSB. To address these questions, we varied T injection concentrations and frequencies in castrated, sexually-experienced Syrian hamsters. All males injected daily with an aqueous vehicle failed to display the ejaculatory reflex 5 weeks after castration. Once daily 15 μg subcutaneous T injections both maintained and restored MSB, whereas once daily 5 μg T injections resulted in fewer males ejaculating and longer ejaculation latencies. Substantially higher T doses were required to restore MSB in previous studies when T was administered in an oil vehicle. 50 μg T maintained MSB in most hamsters injected once every 4 or 7 days, despite long intervals between injections during which circulating T was undetectable or well below physiological concentrations. Some T regimens that maintained MSB were associated with subnormal seminal vesicle and ventral prostate weights. The demonstration that relatively brief, infrequent elevations of T are sufficient to support MSB provides a useful model to assess the neuroendocrine basis of MSB and raises the possibility that infrequent low dose androgen replacement protocols may restore sex behavior to hypogonadal men without inducing some of the negative side-effects associated with more frequent, higher dose treatments.
Male sex behavior (MSB) of mammals depends on gonadal androgen secretion (Meisel and Sachs, 1994, Hull et al., 2002, Hull et al., 2006 and Hull and Dominguez, 2007); copulatory behavior declines in the absence of testosterone (T) and is restored with T replacement. T replenishment typically has been achieved in rodents by implanting constant release capsules or injecting steroid hormones dissolved in oil vehicles. In rats a single intramuscular injection of 100 μg testosterone propionate elevated T concentrations above the physiological range for 24 h; residual hormone was present in the blood as long as a week after injection (Keating and Tcholakian, 1983). Lingering effects of several days duration have also been reported in rats after a single subcutaneous administration of non-esterified T dissolved in soybean oil (Gerrity et al., 1982). The episodic ultradian rhythms of T secretion of intact rodents are not mimicked by replacement procedures that chronically elevate circulating hormone concentrations (capsules, Damassa et al., 1977) or injections that generate T concentrations well above the physiological range (73 ng/ml in a typical replacement regimen compared to 2 ng/ml in intact male Syrian hamsters; Arteaga-Silva et al., 2005). In mice and rats, T remains at low basal values except for several fleeting surges each day (Coquelin and Desjardins, 1982 and Ellis and Desjardins, 1982, respectively). In Syrian hamsters, Mesocricetus auratus, T concentrations are elevated for 4 h in the late subjective day ( Pieper and Lobocki, 2000). Chronic exposure to hormones in typical replacement paradigms may desensitize target tissues ( Wolf et al., 1993) and influence receptor dynamics; low or hormone-free intervals, timing of hormone secretion, and hormone availability in target tissues are important considerations in deconstructing hormone–behavior relations. Duration and frequency of T secretion may be as salient as the amount of available T.
Park et al. (2007) infused Syrian hamsters daily with 100 μg T over 4 h or 50 μg T in each of two 4-hour infusions separated by 8 h. Both regimens maintained MSB despite rapid clearance of circulating T after infusions were terminated. The authors concluded that basal concentrations of T sustained by the gonads during inter-pulse intervals probably are unnecessary for maintenance of MSB. In the present study we employed subcutaneous injections of T dissolved in an aqueous vehicle to elevate blood T concentrations for only a few hours after each injection (e.g., Taylor et al., 1989 and Taylor et al., 1990). No exogenous treatment can exactly simulate endogenous patterns of T secretion, but this regimen appears to be more representative of the natural condition than those typically employed.
We sought to determine the lowest dose of T necessary to maintain and restore the ejaculatory reflex in castrated Syrian hamsters. Injection frequencies were manipulated to determine if MSB is sustained by infrequent treatments followed by long intervals during which T concentrations are either undetectable or well below physiological values. Answers to these questions may increase understanding of fundamental hormone–behavior relations.
