生体内ラット ?? 丸における前駆SteroidsからのAndrogenの生成

II.Progesterone-4-C¹⁴の ?? 丸内連続注入によるAndrogen生成と下垂体剔出或はHCG投与の影響

抄録

To investigate the androgen-biogenesis of rat testis in vivo, a new efficient method for administration of the precursor, named "Inratesticular Infusion Method" (abbr. ITI), was devised (Fig. 1). Compared to the intravenous injection of the precursor1), this was much useful for tracing of the intermediates and for investigation of the action mechanism of gonadotrophin. In this report, progesterone-4-C¹⁴ was given to eviscerated adult rats by ITI (1 μc=0.1 ml/hr. for 1 hr.), and the effects of HCG and hypophysectomy on the androgen-biogenesis were studied. Eight radioactive steroids including unidentified ones were detected in the infused testis, and their concentrations are given in Table 1. Since the main pathway from progesterone to testosterone, i. e. ce-hydroxyprogesterone (17-OHP) → androstenedione testosterone, has already been established by in vitro experiments4-6), the concentrations of only these member steroids were questioned for the discussion (Figs. 2 & 3).
(1) Effect of hypophysectomy : The steps later than progesterone in the testosterone-biogenesis system (abbr. TGS) seems to be impared almost evenly by hypophysectomy, although a slight tendency of relative accumulation of androstenedione is observed in the course of regression. Series of HCG(S) groups (Fig. 2, lower row) might indicate a picture of regression in the maximum capacity of the functioning TGS after hypophysectomy. At the 10 post-operative day, the most of TGS is impared and its immediate responsiveness to HCG is mostly abolished. This impared TGS, however, can be restored by a long period administration of HCG and again produces testosterone.
(2) Effect of RUG: Single injection of HCG to either normal or partial impared TGS, increases concentrations of 17-OHP and testosterone strikingly, but not that of androstenedione. As was already pointed out in our previous reports1, 7), the increased concentration of testosterone in the testis was regarded as the outcome of the increased synthesis accompanying with the secretion, but not a mere accumulation due to suppression of its release. In this point of view, the following deduction might be drown from Fig. 2 : a) HCG action is related even to the process later than progesterone, and it accelerates the steps of both progesterone→17-OHP and androstenedione→testosterone; b) The step between 17-OHP and androstenedione is little influenced by HCG, and also this seems much slower phase than the steps progestrone→17OHP and androstenedione → testosterone. Thus the concentration of androstenedione might be low and not changed by HCG stimulation. (3) In the shorter infusion experiments, as shown in Fig. 3, a picture of presumed ealier conversion, i. e. relative high concentrations of the intermediates, is seen. Furthermore, the accelerated steps of TGS by HCG are well indicated in comparison between the cases treated with and without HCG (Fig. 3., ITI. O. 5 hr.).