The effect of reduced rate of growth on maturation of the male reproductive system of the albino rat.код для вставкиСкачать
T H E E F F E C T O F REDUCED RATE O F GROWTH ON JIATURATION O F T H E MALE REPRODUCTIVE SYSTEJI O F T H E ALBINO R A T ' GEORGE B. TALBERT AND JAMES B. HAMILTON Department of Anatomy, State Universit!] of New Y o r k College of Xedicine at iVew Pork City, Brooklyn, N . P. THREE FIGURES The pioneer work of P. E. Smith ('26, '27) demonstrated that secretions of the pituitary gland produce precocious maturation of the ovaries of the laboratory rat. Subsequently, the role of the anterior lobe of the pituitary gland in effecting such maturational changes in the testes and ovaries of different mammals has been studied extensively. The pituitary glands of rats as young as 1 2 days of age are capable of secreting gonadotrophin (Harris and Jacobsohn, '52). Since the pituitary gland is able to secrete gonadotrophins, and the gonads can respond to such stimulation, much earlier than the age a t which maturation occurs normally, it seems apparent that maturatioii is controlled by still more antecedent factors. The present data pertain t o the relationship in the albino rat between body growth and maturation as judged by the growth of the testes, semiiial vesicles, and ventral prostate and by the initial appearance of spermatozoa in the seminiferous tubules. The body growth was controlled by quantitative restriction of the intake of food. Many studies have been made on the effect of reduced caloric intake upon the growth of the testes and other body organs (Jackson, '15 ; Winters, Smith, illendel, '27 ; and Stewart, This study is a by-product of work supported in p a r t by a research grant (A-89) from the r a t i o n a l Institute f o r Arthritis aiid Metabolic Diseases, of the National Institutes of Health, Public Health Service. 763 764 GEORGE B. TALBERT A K D J A M E S B. HAMILTOR '16, '18). F o r the most p a r t these studies have involved such severe dietary restriction that little or no growth mas perinitted f o r extended periods of time. In the present investigation the restricted animals were allowed to gain weight a t a regular but reduced rate. MATERIALS AS11 hIETHODS The r a t s used in this study were all inales of T i s t a r stock which were raised in our laboratory. In order to standardize the weight at weaning, litters were reduced to '7 animals within 48 hours after birth. Animals wei-e weaned at 20 days of age and only those which weighed 43 to 49gm at 25 days of age were included in the experiment. The r a t s froni each litter which were within the above weight range were separated into two groups. Growth of of first group was made to conform to a standard curve which had been established i n a preliminary experiment. This curve extended from weaning until 57 days of age and v a s based on the r a t e of growth of 25 male r a t s obtained from 6 litters, each containing 7 animals. During this period a uniform rate of growth was maintained by slight restriction in the amount of food made available to the faster growing animals in the group. By this procedure a curve was derived which can be followed by all our rats except those that g' row at an especially slow rate. In the second group the daily increment of growth was reduced t o one-third of that in the first group by limiting the food intake beginning at 25 days of age (fig. 1). These curves were extrapolated a s a guide for controlling the growth of the animals which exceeded 5'7 days of age. The r a t s were weighed daily arid were given their food ration at approximately the same time each day. No animal was fed less than 5 g m of food per day. The aiiiinals were kept i n a room maintained at 25°C. ivith 30% relative humidity. By adherence to these procedures all the r a t s were * Obtained f r o m Carworth Farms. REDUCED G R O W TH A N D MATURATION 765 maintained within three gm of the desired weight throughout the period of study. The animals were autopsied at two t o 5 day intervals as indicated in figures 2 and 3. At autopsy the testes, seminal vesicles, and ventral prostate, along with other organs which are not included in this report, were stripped of grossly visible fat and weighed on a torsion balance. Fluid was re- AGE IN DAYS Fig. 1 Growth curves of rats with normal and quantitatively-restricted food intake. moved from the seminal vesicles prior t o weighing. A representative series of organs were fixed for histological study and stained with hematosylin and eosin. The seminiferous tubules of the testes were examined f o r the presence of spermatozoa. RESULTS Growth of the testes, seminal vesicles, and ventral prostate is graphed separately in relation to (1) age and ( 2 ) body 766 GEORGE R. TALBERT A B D JAMES B. HAMILTON weight. Weights of these organs in the growth-retarded animals autopsied a t 76 and 96 days of age are not included in figures 2 and 3 where organ weight is plotted against age because data were not obtained at comparable ages in the standard group. Testis. I n absolute terms the rate of testicular growth was decreased considerably by reduction in the rate of growth of the body (fig. 2). Relative to body weight, however, the testes of the animals on a restricted diet were larger than those of control animals with the same body weight until a body weight of 150gm was attained. Testicular weight is related to both age and body weight during the period of maturation (fig. 2). Histological study showed that spermatozoa appeared initially in the lumen of the seminiferous tubules at 32 to 35 days of age in both the restricted and control groups. At this age the body weights of the animals were 55 to GO p i in the restricted group and 76 to 90gm in the control group whereas the testes weighed 500 to G50mg in the restricted group and 575 to 875 mg in the control group (figs. 1 and 2 ) . At successively older ages the quantity of spermatozoa in the seminiferous tubules appeared t o increase at the same rate in spite of the fact that the testes weight and body weight of the two groups became increasingly divergent (figs. 1 and 2). Under the conditions of this experiment the maturation of spermatozoa in this species is closely related to the age of the animal. Testis weight cannot be used as an accurate index of the maturational status of the spermatozoa and body weight is even less closely related. Seminal vesicles and ventral prostate. Reduction of the rate of body growth markedly delayed the growth of the seminal vesicles and ventral prostate after 40 days of age (fig. 3). The period of rapid maturational growth which occurs at this time in the control animals did not appear until after 55 days of age in the group with restriction of food. 767 REDUCED GROWTH AND MATURATION h % P 0 Y 3 . i * Y .OQ 4 -3 0 - 0 4 0 0 I. 0 s 0 0 0 R) 0 0 0 0 8 N SWVUOllllN NI 0 0 0 1H9l3M SllS31 8 Y) -8 te i;;g . Y 3 768 t GEORGE B. TALBERT A N D J A M E S B. H A M I L T O N O--RESTRICTa) b--STANDARD o --RESTRICTED A --STANDARD 2001 200 o--RESTRICTED 0--RESTRICTED b--STANDARD A --STANDARD 2 160E t -1 s 5 IZO- 4 . 1 Jo 36 40 AGE 4 4 45 50 IN DAYS I ++I4 4ii 0 b 4 4 4 55 60 6! 50 75 100 125 /50 175 BODY WEIGHT IN GRAMS 200 2f5 Fig. 3 Change i n weight of the ventral prostate and seminal vesicles of rats with normal and restricted food intake in relation to age and body weight. Vertical lines indicate standard error of the mean. REDUCED GROTVTII A N D M A T U R A T I O N 769 Relative to body weight, these organs were larger in dieted than in control rats after a body weight of 100gm was attained. I n this connection it should be appreciated that the dieted animals mere older than the control animals by the time they had attained the same body weight. The similarity in rates of growth between prostate and seminal vesicles in dieted animals (fig. 3) is noteworthy because the threshold for responsiveness to androgens is lower in the prostate than in the seminal vesicles (Callow and Deansley, '35; Moore and Price, '38) and in normal animals there is a rapid increase in rate of growth in the prostate before a similar increase occurs in the seminal vesicles. That prostate and seminal vesicles mature at the same slow rate upon restriction of food is open to several interpretations, one of which is that testicular secretions are not maintained for any noticeable length of time at levels that stimulate more rapid growth of the prostate than of the seminal vesicles. DISCUSSION Restriction of food t o the extent that the increase in body weight of meanling rats proceeded at only one-third that of the control animals resulted in retarded maturation of secondary sex organs. It did not eliminate stimulation of these organs nor delay the maturation of sperniatozoa in the seminiferous tubules ; both of these phenomena occur in severe inanition (Stone, '24). Possible explanations of the failure t o delay the initial appearance of spermatozoa are that spermatogenesis (1) was initiated before the diet was restricted and ( 2 ) is relatively resistant t o a moderate reduction in food intake. There is evidence that spermatogenesis in the rat begins prior to the age when the diet of our animals was restricted. The time required for spermatogenesis in the rat is estimated to be 16 days (Roosen-Runge, '51), 20 days (Leblond and Clermont, '52) and 26 days (Shaver and Mason, '50). An estimate of 20 days would place the initiation of sperniatogenesis at no later 770 GEORGE B. TALBERT A S D J A M E S B. HAMILTON than 15 days in these rats. The supply of food was not restricted until the animals were 25 days old. At present it is not possible to define the mechanisms by which restriction of food delays the age at which secondary sex organs become mature. Many possibilities exist, including the following factors which are known to influence maturation : 1. Lack of foodstuffs necessary f o r growth of the secondary sex organs. 2. Effect of reduced supply of foodstuffs upon the production of gonadotrophins and androgens and perhaps upon centers in the nervous system which control the pituitary gland. 3. The mass of the body (van Wagenen, '49). 4. The amount of depot fat (Bruch, '39; Reynolds, '46). 5. Adrenocortical secretions (Wilkins and Cara, '54 ; Richter and Uhlenhuth, '54). Whereas growth of most non-reproductive organs is dependent primarily on the amount of food utilizable for growth, the reproductive organs are dependent not only on the availability of food but also on the quantity and quality of hormones necessary for stimulation of their growth. I n severe inanition, secretion of gonadotrophins appears t o be reduced (lllulinos and Pomerantz, '41 ; Jlason and Wolfe, '30 ; Meites and Reed, '49). If the amount of gonadotrophin is decreased by the degree of dieting in our series of animals this reduction was not severe enough to delay significantly the appearance of mature spermatozoa. The decreased rate of growth of seminal vesicles and prostate is probably produced by a failure of androgenic stimulation. Reduced androgenic stimulation appears t o be the indirect result of reduced stimulation of the testes. Such an effect has been clearly demonstrated in adult rats subjected to severe inanition. The secondary sex organs retain responsiveness t o androgens even in states of severe starvation (Xoore and Samuels, '31 ; illulinos and Pomerantz, '41). REDUCED G R O W T H A N D M A T U R A T I O N 771 Body size (weight and length) can be a decisive factor in retardation and acceleration of the onset of maturation (Hildebrand, '32; Engle et al., ' 3 7 ; Bogart and associates, '40; van Wagenen, '49). Whether the influence of body weight upon the initiation and completion of maturation is due to size and function of the lean mass, of the amount of body fat, or both is not clear. It is known that fat individuals mature precociously (Bruch, '39; Reynolds, '46) and that increments in depot fat are significantly correlated with augmented titers of ketosteroids and androgens (Hamilton, '54) during certain periods of the lifespan. SUMMARY A study was made in male albino rats o n the effect of body growth on the age at maturation. By restriction of the amount of food, beginning at 25 days of age, the growth rate of the body was reduced to one-third of that of control rats allowed to eat almost nd libitum. The absolute rate of growth of testes, seminal vesicles, and ventral prostate was also reduced although all three organs were considerably larger than in control animals of the same body weight. Spermatozoa appeared initially in the seminiferous tubules at the same age in dieted and control groups. It is concluded that reduction in growth, as regulated by restriction of food to the extent and at the ages employed in this experiment, slowed the completion of maturation of the secondary sex organs, but did not delay the initial appearance of spermatozoa in the seminiferous tubules. I n the animals with restricted intake of food the rate of maturation became similar in both prostate and seminal vesicles. This is in contrast to the more rapid growth of the prostate than the seminal vesicles in control animals and seems noteworthy in view of the lower threshold of response to androgens that characterizes the prostate. 772 GEORGE B. TBLBERT A N D J A M E S B. 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