Effect of Methandrostenolone on Growth and Feed Conversion in Cockerels and Pullets

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T. W. SULLIVAN AND J. R. KINGAN

REFERENCES Association of Official Agricultural Chemists, 1945. Official and Tentative Methods of Analysis. 6th ed. Published by the Association of Official Agricultural Chemists, Washington, D. C. Blaylock, L. G., L. H. Neagle and C. F. LeFevre, 1961. Studies on the calcium and phosphorus requirements of growing turkeys. Poultry Sci. 40: 1381. Duncan, D. B., 19S3. Significant tests for differences between ranked treatments in anlaysis of variance. Technical Report No. 3, Dept. of Statistics, Virginia Agri. Expt. Sta., Blacksburg, Va. Formica, S. D., M. J. Smidt, M. M. Bachrach, W. F.

Davin and J. C. Fritz, 1962. Calcium and phosphorus requirements of growing turkeys and chickens. Poultry Sci. 41: 771-776. National Research Council, 1960. Nutrient requirements for domestic animals. No. 1. Nutrient requirements for poultry. Pensack, J. M., and R. H. White-Stevens, 1961. The calcium and phosphorus requirement of the turkey poult. Poultry Sci. 40: 1443. Slinger, S. J., W. F. Pepper, I. Motzok and I. R. Sibbald, 1961. Studies on the calcium requirements of turkeys. 1. Influence of antibiotics during the starting period. 2. Interrelationship with reserpine during the growing period. Poultry Sci. 40:1281-1291. Snedecor, G. W., 19S6. Statistical Methods. 5th ed. The Iowa State College Press, Ames, Iowa. Standlee, W. J., R. E. Davies, C. W. Deyoe and J. R. Couch, 1962. Turkey prestarter inorganic phosphorus and calcium allowances. Poultry Sci. 41:1685. Stephenson, E. L., K. E. Rinehart and D. B. Bragg, 1962. Calcium-phosphorus requirement for dayold poults. Poultry Sci. 41: 1686. Sullivan, T. W., and J. R. Kingan, 1962. Calcium: phosphorus ratio, phosphorus and vitamin D s interaction and requirements for turkeys 0-6 weeks of age. Poultry Sci. 41: 1687. Sullivan, T. W., and Y. Y. Al-Ubaidi, 1963. Linear growth and mineralization of bones in Broad Breasted Bronze turkeys. Poultry Sci. 42: 46-49.

Effect of Methandrostenolone on Growth and Feed Conversion in Cockerels and Pullets G E O R G E B. B E L L O F F 1 AND B E B E H S U

CIBA Pharmaceutical Company, Summit, New Jersey (Received for publication January 31, 1963)

INTRODUCTION

ANDROGENS, more specifically, tes•L*- tosterone and some of its derivatives, have been shown to stimulate protein anabolism in man, rats, cattle, rabbits, and dogs (Bergetrand, 1950; Burris et al., 1954; Kenyon, 1938; Kim 1

Present address: Feed Additive Research, Animal Health Division, Schering Corporation, Bloomfield, New Tersev.

et al., 1952; Kochakian et al, 1935, 1950; Light and Tornaben, 1953; Perlman and Cassidy, 1953; Rupp and Paschkis, 1954; Shay et al., 1941). Their use as anabolic agents in chickens has not been particularly productive. Evidence to date in poultry suggests that androgens have neither improved feed efficiency nor growth rate. Depending upon the dose level, they have either

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Norfolk, Virginia. The authors are grateful to C. W. Swingle and Co., Lincoln, Neb. for supplying the stabilized white grease; to the Smith-Douglass Co., Inc., Norfolk, Va., for supplying the dicalcium phosphate; to the Calcium Carbonate Co., Quincy, 111. for supplying the calcium carbonate; to E. I. Du Pont de Nemours and Co., Wilmington 98, Del. for supplying the methionine-hydroxy-analog and to Merck and Co., Inc., Rahway, N. J. for supplying the penicillin-streptomycin used in this study.

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METHANDROSTENOLONE

Studies in cockerels by Jaffe (1961)

OH

J CH3

A/\/ 0 FIG. 1. A^iya-Methyltestosterone; Methandrostenolone Dianabol®

showed that 2.75 mg. of methandrostenolone per kg. of diet fed from 0-5 weeks of age had no effect on growth rate or on weight of the testes. Preliminary studies in our laboratories suggested that the range of 0.625 to 2.50 mg./kg. of diet would be worth further exploration (Belloff and Hsu, unpublished data). Since these were small scale battery studies, it was our belief that larger samples of the population should be used in experiments simulating actual field conditions. Consequently, experiments were initiated with larger numbers of broiler chicks reared in floor pens. The following is a report of these explorations. MATERIALS AND METHODS

A block of twelve pens, six in a row placed back to back, were utilized in this study. Wire partitions separated one pen from the other. Each pen was nine feet deep and ten feet wide. Since air was exhausted at one end of the block of pens and fresh air admitted by louvers at the other end, there was a possibility of a temperature differential from one end to the other end of the block of pens. Thus, the twelve pens were divided for purposes of assigning treatments into three groups of four; a middle group and two end groups, each group consisting of four pens back to back. Two separate experiments were conducted, the first involved cockerels, the second pullets. In the first experiment,

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reduced growth in the cockerel or have had little, if any, effect (Adams and Herrick, 1955; Anderson, 1953; Libby et al., 1953; Moreng and Bryant, 1956). In the pullet, the reports show no effect on gain (Anderson, 1953). In surgical capons, rate of gain has been stimulated by androgens (Libby et al., 1953). Desaulles (Desaulles et al., 1959) explored a new anabolic agent, methandrostenolone (Dianabol®) (see Figure 1) and found it to possess greater anabolic and lower androgenic activity when compared with testosterone propionate, 17a-methyltestosterone and other androgens. His studies also revealed that the steroid increased body weight gain in the castrated adult male rat. The stimulation of body weight gain was confirmed by nitrogen balance experiments. It was found to be similarly effective in man (Liddle and Burke, 1960). Studies in rats have shown methandrostenolone to exhibit anti-inflammatory activity under certain conditions of experimental inflammation (Renzi and Chart, 1962). Methandrostenolone augmented the responses to corticosteroid therapy in patients with rheumatoid arthritis (Clark and Mills, 1962) as well as in animals (Kuzell et al., 1962). Investigations in the human field (Liddle and Burke, 1960; Clark and Mills, 1962; Kuzell et al., 1962) indicate that methandrostenolone is of value as an anabolic agent in disease states, particularly, in those conditions where the human patient is in nitrogen imbalance. These studies in man and animals suggest that the lower androgenic activity of this compound coupled with its anabolic and limited anti-inflammatory properties would make it worthy of exploration in poultry as a growth stimulant, both in the presence and absence of the disease state.

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G. B. BELLOIT AND B. H S U

TABLE 1.—Methandroslenolone cockerel study {mean body weight1 and feed conversion data) Methandrostenolone treatments (mg./kg. of diet) Control 0.625

Age in weeks

4 9 1 2

Body wt. (gm.)

Feed conversion2

Body wt. (gm.)

616 1,908

1.73 2.28

606 1,895

Based on means of 3 pens of 100 birds. Total feed consumption to date Total body weight to date

1.25

Feed Body conversion2 wt. (gm.) 1.74 2.29

606 1,878

2.50

Feed conversion2 1.76 2.31

Body Feed wt. (gm.) conversion2 618 1,905

1.70 2.31

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twelve, hundred one-day old Cobb Creek pullets. The same experimental design and White Rock cockerels were randomly facilities were used in this study as were distributed equally among the twelve pens employed in the previous experiment. In by means of a table of random numbers. addition to sex, there were two changes The following four treatments were al- (a) a different source of chicks and (b) lotted by random distribution to each pullets were wingbanded and initially group of four pens: non-medicated con- weighed at three days of age with medicatrols, 0.625,1.25 and 2.50 mg. methandros- tion starting on the third day instead of tenolone per kg. of diet; thus, the four day four as in the previous experiment. Pen weights were taken at two weeks of treatments were replicated three times. age and subsequent weighings were made At four days of age, the birds were indiat weekly intervals thereafter. Feed convidually weighed, wingbanded and mediversions and average body weights are cation administered for the first time. At two weeks of age the birds were weighed recorded in Table 2. for the first time after medication had RESULTS AND DISCUSSIONS been initiated and weighings were made at weekly intervals thereafter. All weighings The present studies differ from those of were made on a pen weight basis. Feed Jaffe (1961) and Howes (1962) in that our consumption and pen weights were re- experiments were conducted in floor pens corded at each weighing. Average body and heat was supplied by infra-red lamps. weight and feed conversion were com- Furthermore, while Jaffe fed methandrosputed (see Table 1). tenolone for five weeks only and limited his study to the cockerel and one dose Heat was supplied for the first three weeks by means of infra-red lamps. Wood level, our studies included both the cockshavings were used for bedding. A corn- erel and the pullet, extended the feeding soybean oil meal diet was fed throughout period to nine weeks of age, and employed the experiment. It contained no antibi- three dose levels. Our highest dose (2.50 otics, coccidiostats or treatments other mg./kg. of diet) most closely approxithan those noted in the experimental mated the dose employed in Jaffe's study. design. It was calculated to contain 23.4% Although our experimental conditions protein, 7% fat, 2.6% fibre and a Calorie- differed, we, too, found no growth stimulation at five weeks of age, nor at the end protein ratio of 43.5 to 1. A second trial was conducted in twelve, of the nine week growing period. Statistical analyses were run on the hundred-day-old Van Tress Arbor Acre

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METHANDROSTENOLONE TABLE 2.—Methandrostenolone pullet study (mean body weight1 and feed conversion data) Methandrostenolone treatments (mg./kg. of diet) Control 0.625

Age in weeks Body wt. (gm.) 4 9 1 2

506 1,401

Feed conversion2 1.58 2.20

Body wt. (gm.) 503 1,408

1.25

Feed Body conversion2 wt. (gm.) 1.61 2.21

505 1,416

2.50

Feed Body conversion2 wt. (gm.) 1.59 2.21

510 1,417

Feed conversion2 1.62 2.23

data collected in these experiments. The convalescent period in such diseases as data pertinent to body weight consisted of chronic respiratory disease complex three replicates of 100 birds each per should receive specific attention. treatment. Each replicate was recorded on CONCLUSIONS a pen weight basis. From the number of The effect of methandrostenolone on birds per pen and the pen weight, the average bird weight was computed, and body weight gain and feed efficiency was from these data the analysis of variance studied in two separate experiments, one and " t " tests were used for the comparison in cockerels, the other in pullets. When of the average final body weights of nine feed medication was initiated at three or week old chickens. No significant differ- four days of age, there was no significant ences were found between the controls and difference in final average body weight between non-medicated controls and birds each treatment mean. receiving 0.625, 1.25 or 2.50 mg. of methOur results differ from those of Howes androstenolone per kg. of diet for a period (personal communication) who obtained a of 63 consecutive days. growth response with methandrostenolone when infra-red lamps and heat coils were REFERENCES used as different sources of heat. The re- Adams, J. L., and R. B. Herrick, 1955. Interactions sponse to methandrostenolone was greater of the gonadal hormones in the chicken. Poultry Sci. 34: 117. in the heat coil groups than in the infrared lamp groups. It may be that the condi- Anderson, C. L., 1953. Effect of testosterone on pullets. Poultry Sci. 32: 883-884. tions under which the birds were raised Belloff, G. B., and B. Hsu, Unpublished data. were contributing factors, i.e., floor vs. Bergetrand, C. G., 1950. The influence of testosterbattery and infra-red lamps vs. electric one propionate on skeletal development in the immature rabbit. Acta Endocrin. 4: 91. heating coils. Healthy birds in a good state of nutri- Burris, M. J., R. Bogart, A. W. Oliver, A. O. Mackey and J. E. Oldfield, 1954. Rate and efficiency of tion were used in the present experiments, gains in beef cattle. 1. Response to injected tesfurther studies should be undertaken to tosterone. Oregon Agr. Exp. Sta. Tech. Bui. determine the effect of methandrostenoNo. 31. lone on growth and feed efficiency in Clark, G. M., and D. Mills. 1962. Corticosteroid therapy of rheumatoid arthritis supplemented healthy animals when lower levels of with Methandrostenolone. Arthrit. Rheum. 5: protein are employed in the diet, more 156. specifically various levels of the different Desaulles, P. A., C. Krahenbuhl, W. Schuler and amino acids. Its effect on the recovery and H. J. Bein, 1959. Experimental study on Diana-

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Based on means of 3 pens of 100 birds. Total feed consumption to date Total body weight to date

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G. B. BELLOEF AND B. H S U Libby, D. A., P. J. Schaible, J. Meites and E. P. Reineke, 1953. Value of progesterone and estradiol on growth and finish in broilers. Poultry Sci. 32: 1086-1088. Liddle, G. W., and H. A. Burke, Jr., 1960. Anabolic steroids in clinical medicine. Helv. Med. Acta. 27: 505-513. Light, A. E., and J. A. Tornaben, 1953. Effects of prolonged percutaneous administration of methyl testosterone and estradiol on growing male rats. Biol. Abs. 27: 222-232. Moreng, R. E., and R. L. Bryant, 1956. Body weight gains and dressing loss as affected by breed in diethylstilbesterol treated males. Poultry Sci. 35: 672-674. Perlman, P. L., and J. W. Cassidy, 1953. Influence of nitrogen intake on nitrogen-retaining action of testosterone propionate. Proc. Soc. Exp. Biol. Med. 83: 674-675. Renzi, A. A., and J. J. Chart, 1962. Interaction of methandrostenolone and adreno cortical hormones. Proc. Soc. Exp. Biol. Med. 110: 259-262. Rupp, J. J., and K. E. Paschkis, 1954. Influence of testosterone propionate on protein metabolism of thyroidectomized rats. Proc. Soc. Exp. Biol. Med. 86: 399-401. Shay, H. J., Gerhson-Cohen, J. Paschkis and S. S. Fels, 1941. Influence of testosterone propionate on somatic growth in the white rat. Endocrin. 28: 877.

Effect of Photopenod on the Response of Developing Pullets to Different Nutritional Treatments1 LAWRENCE R. BERG, REED S. HANSEN AND GORDON E. BEARSE Washington State University, Western Washington Experiment Station, Puyallup (Received for publication January 31, 1963)

A

PREVIOUS report from this laboratory (Berg and Bearse, 1961), indicated that restricting feed intake of pullets to 83 percent of ad libitum consumption from 8-21 weeks of age did not retard sexual maturity or affect subsequent rate of lay when the pullets were subjected to 1

Scientific paper No. 2308, Washington Agricultural Experiment Stations, Pullman. Project No. 1241.

constant nine hours of light per day during the same period. This was in contrast to the results of Sunde et al. (1954), Milby and Sherwood (1956), Tomhave (1958) and Maclntyre and Aitken (1959) who found that restricted feeding retarded sexual development. The results of these investigators were obtained with winter or spring hatched pullets which matured under increasing or long day length.

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bol, a new anabolic agent. Schweiz. Med. Wschr. 89: 1313. Hebert, B. A., and C. C. Branson, 1956. Effect of sex hormones on the fat and moisture content of broiler carcasses. Poultry Sci. 35: 1147. Howes, J. R., 1962. The possibilities of orally administered anabolic steroids for growth stimulation in chicks. Proc. Assn. So. Agr. Workers 59th Annual Convention. 244-245. Howes, J. R., Personal communication. Jaffe, P., 1961. The effect of feeding a steroid hormone (Methandrostenolone) to chicks. Poultry Sci. 40: 1183-1185. Kenyon, A. T., 1938. The effect of testosterone propionate on the genitalia, prostate, secondary sex characters, and body weight in eunuchoidism. Endocrin. 23: 121. Kim, K. S., D. F. MaGee and A. C. Ivy, 1952. Mechanism of difference in growth rate between male and female rats. Am. J. Physiol. 169: 525. Kochakian, C. D., and J. R. Murlin, 1935. Effect of male hormone in protein and energy metabolism of castrate dogs. J. Nutrition, 10: 437-459. Kochakian, C. D., E. Robertson and M. N. Bartlett, 1950. Sites and nature of protein anabolism stimulated by testosterone propionate in the rat. Am. J. Physiol. 163: 332. Kuzell, W. C , R. P. Glover, D. L. Bruns and J. 0. Gibbs, 1962. Methandrostenolone in rheumatic diseases and osteoporosis. Geriatrics, 17: 428.