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Notes: Abstract: Male Syrian hamsters that were exposed for 8 weeks to short photoperiod (LD 10:14) or treated with melatonin in the late afternoon under long photoperiod conditions (LD 14:10) had a significantly higher content of androgen receptors in the Lipidex-purified soluble fractions isolated from the Harderian glands as compared to the long photoperiod (LD 14:10) exposed controls. Simultaneous computer-assisted analyses of all series of saturation and competition experiments revealed that the numerical value of the apparent Kd, as determined by using the synthetic androgen R-1881 (methyltrienolone), was not different between the experimental groups, and ranged from 0.050 to 0.067 nM. Of the principal natural androgens, testosterone (T) was most potent in inhibiting methyltrienolone binding to the receptor (Ki values from 0.33 to 0.55 nM), and 5α-dihydrotestosterone (DHT) and α4-androstenedione (AD) were less effective (Ki values between 1 and 1.9 nM). In the hypothalami and pituitaries of the same animals, used in parallel control assays, DHT was twice as potent as T. Short-term castration (24 hr post-orchidectomy) did not result in significant changes in the receptor binding characteristics. Following 8 weeks exposure to a long photoperiod (LD 14:10) the Bmax values demonstrated a four-fold increase in castrated animals (179 fmoles/mg protein vs. 47 fmoles/mg protein) over intact controls. The relative binding affinity of the major androgens under these conditions remained unchanged, with the exception of AD, where a five-fold increase in the numerical Ki values (decrease in the binding affinity) was recorded (Ki = 9.6 nM). Studies on in vitro metabolism of the natural androgens by the cytosol during incubation under conditions identical to those employed in the binding studies revealed that in the normal intact animal AD is metabolized to T in elevated amounts. The ability of the Harderian gland to make this conversion is dramatically diminished following long-term castration. This could explain the apparent “shift” in the high affinity of AD toward a much lower one. Testosterone, however, was not further metabolized. No DHT was formed and small amounts of AD were recovered. Thus, in the androgen receptor system of the hamster Harderian gland testosterone appears to be a strong androgen per se, binding to the receptor with affinity higher than that of DHT. This receptor system is apparently flexible in its response to changes in the photoperiod and to removal of the natural steroids from the endogenous milieu following long-term castration. Both situations are accompanied by a significant increase in receptor numbers, though castration seemingly results in concomitant changes in the androgen metabolism in the gland.