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. 1978 Mar;61(3):624–632. doi: 10.1172/JCI108973

Alcohol-Induced Ovarian Failure in the Rat

David H Van Thiel 1,2, Judith S Gavaler 1,2, Roger Lester 1,2, Richard J Sherins 1,2
PMCID: PMC372574  PMID: 641143

Abstract

The effect of ethanol feeding on ovarian function and structure in female rats was studied in alcohol-fed animals, isocalorically fed controls, and two ad libitum-fed control groups. Ovarian weight was reduced by 60% in alcohol-fed animals compared with the control groups. Gross disruption of ovarian architecture was noted, characterized by the absence of any corpus hemorrhagicum and corpus albicans. Moreover, plasma levels of estradiol were significantly reduced in the alcohol-fed animals (P < 0.01) compared with the levels found in isocaloric controls. Plasma levels of estrone and corticosterone were increased in alcoholfed and isocaloric control animals relative to those of ad libitum-fed animals suggesting a primarily adrenal, rather than ovarian, origin for these two steroids. Despite the increase in estrone, the secondary sex organs (uterus and fallopian tubes) reflected marked estrogen deprivation presumably as a result of estradiol insufficiency.

Progesterone levels in the alcohol-fed animals were significantly less than levels in the isocaloric and intact ad libitum-fed controls but were not significantly different compared to oophorectomized animals.

Plasma follicle-stimulating hormone levels were similar in alcohol-fed, isocaloric controls, and ad libitum-intact controls. They were, however, one-third the level of oophorectomized controls. Both alcohol-fed and isocaloric controls had increased levels of plasma luteinizing hormone, although levels were below those seen in oophorectomized controls (P < 0.01).

The results establish that ingestion of a diet containing 5% ethanol for periods as short as 6 wk produces functional and histologic ovarian failure in the female rat.

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Selected References

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  1. ARON E., FLANZY M., COMBESCOT C., PUISAIS J., DEMARET J., REYNOUARD-BRAULT F. L'ALCOOL EST-IL DANS LE VIN L''EL'EMENT QUI PERTURB'E, CHEZ LA RATTE, LE CYCLE VAGINAL? Bull Acad Natl Med. 1965 Feb 9;149:112–120. [PubMed] [Google Scholar]
  2. ASCHKENASY-LELU P. Action des boissons alcoolisées sur le rendement reproducteur du rat. C R Hebd Seances Acad Sci. 1958 Feb 24;246(8):1275–1277. [PubMed] [Google Scholar]
  3. Abraham G. E., Swerdloff R., Tulchinsky D., Odell W. D. Radioimmunoassay of plasma progesterone. J Clin Endocrinol Metab. 1971 May;32(5):619–624. doi: 10.1210/jcem-32-5-619. [DOI] [PubMed] [Google Scholar]
  4. Badr F. M., Badr R. S. Induction of dominant lethal mutation in male mice by ethyl alcohol. Nature. 1975 Jan 10;253(5487):134–136. doi: 10.1038/253134a0. [DOI] [PubMed] [Google Scholar]
  5. Badr F. M., Bartke A. Effect of ethyl alcohol on plasma testosterone level in mice. Steroids. 1974 Jun;23(6):921–928. doi: 10.1016/0039-128x(74)90064-6. [DOI] [PubMed] [Google Scholar]
  6. Baker H. W., Burger H. G., de Kretser D. M., Dulmanis A., Hudson B., O'Connor S., Paulsen C. A., Purcell N., Rennie G. C., Seah C. S. A study of the endocrine manifestations of hepatic cirrhosis. Q J Med. 1976 Jan;45(177):145–178. [PubMed] [Google Scholar]
  7. Borhanmanesh F., Haghighi P. Pregnancy in patients with cirrhosis of the liver. Obstet Gynecol. 1970 Aug;36(2):315–324. [PubMed] [Google Scholar]
  8. CRANSTON E. M. Effect of tranquilizers and other agents on sexual cycle of mice. Proc Soc Exp Biol Med. 1958 Jun;98(2):320–322. doi: 10.3181/00379727-98-24031. [DOI] [PubMed] [Google Scholar]
  9. Chopra I. J., Tulchinsky D., Greenway F. L. Estrogen-androgen imbalance in hepatic cirrhosis. Studies in 13 male patients. Ann Intern Med. 1973 Aug;79(2):198–203. doi: 10.7326/0003-4819-79-2-198. [DOI] [PubMed] [Google Scholar]
  10. Corrodi H., Fuxe K., Hökfelt T. The effect of ethanol on the activity of central catecholamine neurones in rat brain. J Pharm Pharmacol. 1966 Dec;18(12):821–823. doi: 10.1111/j.2042-7158.1966.tb07817.x. [DOI] [PubMed] [Google Scholar]
  11. DEANE H. W., LOBEL B. L., ROMNEY S. L. Enzymic histochemistry of normal human ovaries of the menstrual cycle, pregnancy, and the early puerperium. Am J Obstet Gynecol. 1962 Feb 1;83:281–294. doi: 10.1016/s0002-9378(16)35833-1. [DOI] [PubMed] [Google Scholar]
  12. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Galvão-Teles A., Burke C. W., Anderson D. C., Marshall J. C., Corker C. S., Bown R. L., Clark M. L. Biologically active androgens and oestradiol in men with chronic liver disease. Lancet. 1973 Jan 27;1(7796):173–177. doi: 10.1016/s0140-6736(73)90005-6. [DOI] [PubMed] [Google Scholar]
  14. Gordon G. G., Altman K., Southren A. L., Rubin E., Lieber C. S. Effect of alcohol (ethanol) administration on sex-hormone metabolism in normal men. N Engl J Med. 1976 Oct 7;295(15):793–797. doi: 10.1056/NEJM197610072951501. [DOI] [PubMed] [Google Scholar]
  15. Gordon G. G., Olivo J., Rafil F., Southren A. L. Conversion of androgens to estrogens in cirrhosis of the liver. J Clin Endocrinol Metab. 1975 Jun;40(6):1018–1026. doi: 10.1210/jcem-40-6-1018. [DOI] [PubMed] [Google Scholar]
  16. Green H. G. Infants of alcoholic mothers. Am J Obstet Gynecol. 1974 Mar 1;118(5):713–716. doi: 10.1016/s0002-9378(16)33745-0. [DOI] [PubMed] [Google Scholar]
  17. Hotchkiss J., Atkinson L. E., Knobil E. Time course of serum estrogen and luteinizing hormone (LH) concentrations during the menstrual cycle of the rhesus monkey. Endocrinology. 1971 Jul;89(1):177–183. doi: 10.1210/endo-89-1-177. [DOI] [PubMed] [Google Scholar]
  18. Jones K. L., Smith D. W., Ulleland C. N., Streissguth P. Pattern of malformation in offspring of chronic alcoholic mothers. Lancet. 1973 Jun 9;1(7815):1267–1271. doi: 10.1016/s0140-6736(73)91291-9. [DOI] [PubMed] [Google Scholar]
  19. Jung Y., Russfield A. B. Prolactin cells in the hypophysis of cirrhotic patients. Arch Pathol. 1972 Sep;94(3):265–269. [PubMed] [Google Scholar]
  20. Kley H. K., Nieschlag E., Wiegelmann W., Solbach H. G., Krüskemper H. L. Steroid hormones and their binding in plasma of male patients with fatty liver, chronic hepatitis and liver cirrhosis. Acta Endocrinol (Copenh) 1975 Jun;79(2):275–285. doi: 10.1530/acta.0.0790275. [DOI] [PubMed] [Google Scholar]
  21. Lieber C. S., DeCarli L. M. Quantitative relationship between amount of dietary fat and severity of alcoholic fatty liver. Am J Clin Nutr. 1970 Apr;23(4):474–478. doi: 10.1093/ajcn/23.4.474. [DOI] [PubMed] [Google Scholar]
  22. Loriaux D. L., Ruder H. J., Lipsett M. B. The measurement of estrone sulfate in plasma. Steroids. 1971 Oct;18(4):463–472. doi: 10.1016/0039-128x(71)90059-6. [DOI] [PubMed] [Google Scholar]
  23. Martin J., Martin D. C., Lund C. A., Streissguth A. P. Maternal alcohol ingestion and cigarette smoking and their effects on newborn conditioning. Alcohol Clin Exp Res. 1977 Jul;1(3):243–247. doi: 10.1111/j.1530-0277.1977.tb05879.x. [DOI] [PubMed] [Google Scholar]
  24. Moss J. N., Smyth R. D., Beck H., Martin G. J. Ethanol impact on brain acetylcholine and its modification by cysteine. Arch Int Pharmacodyn Ther. 1967 Jul;168(1):235–238. [PubMed] [Google Scholar]
  25. Mulvihill J. J., Klimas J. T., Stokes D. C., Risemberg H. M. Fetal alcohol syndrome: seven new cases. Am J Obstet Gynecol. 1976 Aug 1;125(7):937–941. doi: 10.1016/0002-9378(76)90492-0. [DOI] [PubMed] [Google Scholar]
  26. Olivo J., Gordon G. G., Rafii F., Southren A. L. Estrogen metabolism in hyperthyroidism and in cirrhosis of the liver. Steroids. 1975 Jul;26(1):47–56. doi: 10.1016/0039-128x(75)90005-7. [DOI] [PubMed] [Google Scholar]
  27. PINCUS I. J., RAKOFF A. E., COHN E. M., TUMEN H. Hormonal studies in patients with chronic liver disease. Gastroenterology. 1951 Dec;19(4):735–754. [PubMed] [Google Scholar]
  28. Pentikäinen P. J., Pentikäinen L. A., Azarnoff D. L., Dujovne C. A. Plasma levels and excretion of estrogens in urine in chronic lever disease. Gastroenterology. 1975 Jul;69(1):20–27. [PubMed] [Google Scholar]
  29. Randall C. L., Taylor J., Walker D. W. Ethanol-induced malformations in mice. Alcohol Clin Exp Res. 1977 Jul;1(3):219–224. doi: 10.1111/j.1530-0277.1977.tb05876.x. [DOI] [PubMed] [Google Scholar]
  30. Rodbard D., Chrambach A. Estimation of molecular radius, free mobility, and valence using polyacylamide gel electrophoresis. Anal Biochem. 1971 Mar;40(1):95–134. doi: 10.1016/0003-2697(71)90086-8. [DOI] [PubMed] [Google Scholar]
  31. Rodbard D., Lewald J. E. Computer analysis of radioligand assay and radioimmunoassay data. Acta Endocrinol Suppl (Copenh) 1970;147:79–103. doi: 10.1530/acta.0.065s079. [DOI] [PubMed] [Google Scholar]
  32. Russell M. Intrauterine growth in infants born to women with alcohol-related psychiatric diagnoses. Alcohol Clin Exp Res. 1977 Jul;1(3):225–231. doi: 10.1111/j.1530-0277.1977.tb05877.x. [DOI] [PubMed] [Google Scholar]
  33. Sander L. W., Snyder P. A., Rosett H. L., Lee A., Gould J. B., Ouellette E. Effects of alcohol intake during pregnancy on newborn state regulation: a progress report. Alcohol Clin Exp Res. 1977 Jul;1(3):233–241. doi: 10.1111/j.1530-0277.1977.tb05878.x. [DOI] [PubMed] [Google Scholar]
  34. Sherins R. J., Vaitukaitis J. L., Chrambach A. Physical characterization of hFSH and its desialylation products by isoelectric focusing and electrophoresis in polyacrylamide gel. Endocrinology. 1973 Apr;92(4):1135–1141. doi: 10.1210/endo-92-4-1135. [DOI] [PubMed] [Google Scholar]
  35. Smith D. W., Jones K. L., Hanson J. W. Perspectives on the cause and frequency of the fetal alcohol syndrome. Ann N Y Acad Sci. 1976;273:138–139. doi: 10.1111/j.1749-6632.1976.tb52874.x. [DOI] [PubMed] [Google Scholar]
  36. Van Thiel D. H., Gavaler J. S., Lester R., Goodman M. D. Alcohol-induced testicular atrophy. An experimental model for hypogonadism occurring in chronic alcoholic men. Gastroenterology. 1975 Aug;69(2):326–332. [PubMed] [Google Scholar]
  37. Van Thiel D. H., Gavaler J. S., Lester R., Loriaux D. L., Braunstein G. D. Plasma estrone, prolactin, neurophysin, and sex steroid-binding globulin in chronic alcoholic men. Metabolism. 1975 Sep;24(9):1015–1019. doi: 10.1016/0026-0495(75)90094-3. [DOI] [PubMed] [Google Scholar]
  38. Van Thiel D. H., Gavaler J. S., Little J. M., Lester R. Alcohol: its effect on the kidney. Metabolism. 1977 Aug;26(8):857–866. doi: 10.1016/0026-0495(77)90004-x. [DOI] [PubMed] [Google Scholar]
  39. Van Thiel D. H., Lester R. Alcoholism: its effect on hypothalamic pituitary gonadal function. Gastroenterology. 1976 Aug;71(2):318–327. [PubMed] [Google Scholar]
  40. Van Thiel D. H., Lester R., Sherins R. J. Hypogonadism in alcoholic liver disease: evidence for a double defect. Gastroenterology. 1974 Dec;67(6):1188–1199. [PubMed] [Google Scholar]

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