Melengestrol acetate (MGA) -- estrus synchronization
Estradiol17 beta -- early onset of puberty in beef cattle
Steroid use in Australian cattle industry
Trenbolone -- growth, feed efficiency, and carcass composition of steers
Zeranol -- genotoxicity of a synthetic steroid
Clenbuterol -- a non-steroidal liver poison
Unexpected synergy of estrogenic pesticides endosulfan, dieldrin, toxaphene, and chlordane

Estrus Synchronization of Beef Cattle with Melengestrol

David Walker et al., MSU JULY 1992

Melengestrol acetate (MGA), a progestogen-like compound:

Progestogens are synthetic forms of the naturally occurring hormone, progesterone. Progesterone is produced by the corpus luteum [CL]. By negative feedback, it reduces pituitary function, thus preventing a female from coming into heat. When administered in conjunction with a luteolytic agent, such as PGF2a or estradiol valerate, progestogens can provide an effective means of resetting the cow's physiological clock. If the progestogen is administered for several days, an artificial corpus luteum can in effect be installed, which can be removed at the producer's discretion.

Melengestrol plus Prostaglandin F2a:

A synchronization regime involves combining the effects of melengestrol acetate (MGA), a progestogen-like compound, with PGF2a. When administered in the feed at a level of .5 mg. per head per day, MGA is very effective at preventing cows from coming into heat. When PGF2a is administered following MGA removal, cows experience a tightly synchronized estrus.

Melengestrol formula:17a-hydroxy-6-16-methyl-16-methylenepregna-4, 6-diene-3,2-dione


Effectiveness of melengesterol in suppressing estrus and promoting wieght gain

B. C. Allison and R. L. McCraw

Many producers, however, have reservations about summer grazing of heifers their exhibiting estrus. Problems include better fencing required and getting bred if there is a bull nearby. Also, reduced weight gains can be expected. This project tested the effectiveness of Ralgro growth implants and Melengestrol Acetate [MGA] as mineral supplement for suppressing estrus in yearling heifers on a summer grazing program.

Thirty-eight heifers, average weight 562 pounds, were purchased on April 12, 1993 and processed the next morning at the Mountain Research Station in Waynesville, North Carolina. All heifers were given a Lutylase injection a few days later to abort any that might be pregnant. They were grazed on improved mountain pasture until May 4th. The heifers were weighed again on May 5th and the two weights averaged for a starting weight. One group was implanted on May 5th with the growth stimulant Ralgro. One of the two groups that were not implanted received MGA mixed in their mineral supplement. The average daily intake of MGA was .63 mg per head.


EXOGENOUS ESTRADIOL-17-beta STIMULATES ONSET OF PUBERTY IN BEEF HEIFERS

P.D. Schoppee et al. NCSU Animal Sciences, 1994 Annual Report

Lifetime productivity is enhanced if heifers reach puberty by 12 mo of age, conceive at 15 mo of age and calve at 2 yr of age. However, delayed onset of puberty is a problem which continues to plague the cow-calf industry. The goal of our research has been to better understand mechanisms which regulate onset of puberty in heifers so that we may develop strategies which allow the producer to manage the age at which puberty occurs.

The objective of this experiment was to determine whether exogenous estradiol-17-beta , administered as a single intramuscular injection, could induce onset of puberty in 8-mo-old heifers.

Changes in serum concentrations of progesterone (P4) were used to determine whether E2 induced ovulation and onset of puberty. Heifers were considered pubertal if serum progesterone increased above 1 ng/mL for at least four consecutive samples (indicative of a normal luteal phase) and was followed by a decline then a second increase indicative of continued estrous cyclicity.

The mechanism(s) through which puberty is induced must be identified before exogenous estradiol-17-beta can be used as a tool to induce puberty in replacement heifers. Increased luteinizing hormone (LH) release, follicular development and endogenous estradiol-17-beta all precede the first LH surge which induces ovulation during the natural onset of puberty. Exogenous estradiol-17-beta induces release of an LH surge within 12 hr of administration (Schoppee et al., 1994). Whether the induced LH surge induces ovulation in prepubertal heifers may be determined by the stage of follicular development at the time estradiol-17-beta is injected.


Increasing live weight gains in cattle with steroids

For beef from northern Australia to be sold into premium markets, the grazing industry needs to substantially increase annual liveweight gains. There are two research projects: alternate use of oestrogenic and androgenic anabolic steroids and developing a shot which stimulates muscle growth without increasing feed intake. Currently in Australia, anabolic steroids are used as finishing agents to boost liveweights in the final months before slaughter.

Alternating steroids may increase liveweight gains and mould carcass composition for a particular market. Steroids currently in use are either oestrogens or combinations of an oestrogen with an androgen. These stimulate growth by different mechanisms: oestrogens make carcasses fatter while androgens make them leaner. Alternate use of an androgen then an oestrogen may result in sustained stimulation of growth rate.

Are steroids safe? Use of steroids in meat production is controversial despite overwhelming evidence that beef from cattle treated with legal anabolic steroids is safe for humans. To be competitive, Australia must use equivalent or better technologies than its competitors: in the feedlot industry about 90% of cattle fed for non-EEC markets are treated with an anabolic steroid.

A shot that boosts muscle growth may give producers another option to increase liveweight gains. Studies of clenbuterol, a drug which increases the efficiency of muscle growth, confirmed that it is possible to increase growth without increasing food intake in both males and females, whether animals are entire, castrated or spayed. Side-effects of clenbuterol make the drug unsuitable for use in animal production.

This project is supported by the Meat Research Corporation and the Tropical Beef Centre.


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Effect of trenbolone acetate and estradiol implant on growth, feed efficiency, and carcass composition

Perry TC; Fox DG; Beermann DH
J Anim Sci 69: 4696-702 (1991)

The effects of an implant of 140 mg of trenbolone acetate and 28 mg of estradiol (TBA + E2). Trenbolone implanted, called Revalor, anabolic steroid...In Trial 1, one-half were initially implanted with zeranol and reimplanted with trenbolone acetate and estradiol (TBA+E) after 98 d ....


Effects of an estradiol-trenbolone acetate implant on somatotropin and insulin-like growth factor I

Hongerholt DD; Crooker BA; Wheaton JE; Carlson KM; Jorgenson DM
J Anim Sci 70: 1439-48 (1992)

Hereford steers were implanted with 140 mg of trenbolone acetate (TBA) and 28 mg of estradiol-17 beta ....


Genotoxicity of the anabolic drugs trenbolone and zeranol

Scheutwinkel M; v.d. Hude W; Basler
Arch Toxicol 59: 4-6 (1986)

The androgen trenbolone, and the mycoestrogen zeranol, both anabolic drugs, were tested for their genotoxic potential. Test systems were the SOS-chromotest, the rec-assay and the V79 sister chromatid exchange test without and with metabolic activation using rat liver homogenates and primary rat hepatocytes. It is still a matter of debate if trenbolone has carcinogenic properties, because of its cell transforming activity in vitro. Trenbolone, however, did not demonstrate any genotoxic effect in the assays performed. The results obtained for zeranol were also negative.


The genotoxicity of trenbolone, a synthetic steroid

Richold M., Huntingdon Research Centre, Cambs, England
Arch Toxicol 61: 249-58 (1988)

Trenbolone, a synthetic androgen is used as a growth promotant in animal husbandry. Because of its steroidal structure and properties it has been extensively evaluated in a series of in vitro and in vivo assays to assess its genotoxic and initiating properties. Both the parent molecule 17-beta-hydroxy-trenbolone and its metabolite 17-alpha-hydroxy-trenbolone, produced only in cattle, have been tested. 17-beta-hydroxy-trenbolone was not genotoxic


RALGRO (Zeranol)

FDA, DHHS Animal Drug Export; 4673 [Docket No. 96N-0020]

SUMMARY: The Food and Drug Administration (FDA) is announcing that Mallinckrodt Veterinary, Inc., has filed an application requesting approval for export of the animal drug RALGRO (zeranol) implant for cattle to Canada. The product is intended for implanting in the ear of cattle for increased rate of weight gain and improved feed conversion of weaned beef calves, growing beef cattle, feedlot steers, and feedlot heifers, and increased rate of weight gain in suckling beef calves. The application was received and filed in the Center for Veterinary Medicine on December 7, 1995.

Makarechian, M., Arthur, P.F. and M.A. Price. 1991. Effect of postweaning implantation of zeranol and dietary energy level on growth and reproductive performance of replacement beef heifers. Can. J. Anim., Sci. 71: 265-270.
Shoop MC, Rupp GP, Kimberling CV, Bennett BW: K-R spaying, anabolic agent, (Zeranol) and pasturing spayed heifers with steers: their effect on growth of stocker cattle. Proceedings, Western Section, American Society of Animal Science, 35:134-137, 1984.


Harmful effects of pesticides far more potent when mixed

Copyright © 1996 The Associated Press

WASHINGTON (Jun 6, 1996) -- Pesticides that by themselves have been linked to breast cancer and male birth defects are up to 1,000 times more potent when combined, according to a study.

A federal environmental official called the finding "astonishing" and said if it is confirmed in other labs, it could force a revolution in the way that the environmental effects of chemicals are measured.

The study centered on endosulfan, dieldrin, toxaphene, and chlordane, all pesticide chemicals that are known to turn on a gene that makes estrogen in animals. Estrogen is a hormone that controls formation of female organs. A surplus of the hormone has been linked to breast cancer and to malformation of male sex organs.

By themselves, the pesticides have only a very weak effect on the estrogen gene, said John A. McLachlan of Tulane University, leader of a team that tested the chemicals. "If you test them individually, you could almost conclude that the were non-estrogenic, almost inconsequential," he said. "But when we put them in combination, their potency jumped up 500 to 1,000-fold.

McLachlan said it was expected that combinations of the chemicals would be additive; that is, the effects of two chemicals together would equal the sum of the effects of the chemicals alone.

"Instead of one plus one equaling two, we found in some cases that one plus one equals a thousand," he said. The study is to be published Friday in the journal Science. "These findings are astonishing," said Dr. Lynn Goldman, chief of the Environmental Protection Agency's Office of Prevention, Pesticides and Toxic Substances. "The policy implications are enormous about how we screen environmental chemicals for estrogen effects." "It is a very high priority for us to address the implications of this," she said.

The EPA monitors testing of environment chemicals one at a time, said Goldman, and the agency now must consider how to test for effects of chemicals that might combine in the environment. "We test the ingredients that go into the soup individually," she said. The combination effect "is a very, very new issue for us." Endocrinologist Wade Welshons of the University of Missouri told Science: "It's a very important red flag."

In recent years, many researchers have detected signs that certain industrial and pesticide chemicals released into the environment and absorbed by animals and humans may be able to disrupt hormones, perhaps causing cancer or birth defects. Some of the chemical molecules, such as those tested by the McLachlan group, act on the gene that makes estrogen. This can cause cells to produce a surplus of the hormone. Some researchers suggest that in male embryos, this added estrogen may affect formation of the sex organs. Estrogen surplus also has been linked to breast cancer, testicular cancer and lower sperm counts.

Researchers in Florida have found that at a lake where there was a pesticide spill more than half of the male alligators have smaller than normal penises and hormone levels near that of female alligators. In the Columbia River Basin, researchers found that young otters whose livers have absorbed insecticides have penises and testicles half the normal size. And several studies have found that sperm counts have dropped among Europeans men exposed to some of the chemicals.