Document 0gmqk5DZY1EaxBXoQ90Ly3O7d

Science URL 05103 Nor should it be assumed that scientific results and hypotheses, elaborated from within the various subdisciplines in cancer research, are hatched in a vacuum. Epidemiolo gists sometimes borrow fearlessly From scientists at the bench in framing new hypotheses. Likewise, bench scientists are better informed when they realize the trends that epide miologists can tease out of massive data from population studies. Ultimately, public health policy planners don't give a hoot for the mechanisms underlying a disease. Their goal simply is to reduce dis ease incidence. Thus, NRC's policy recommendations inevitably didn't and couldn't take into account much that is currently exciting in funda mental research on cancer. Regardless of such drawbacks, however, somebody must deal with public health policies, especially those relating to diseases such as cancer. NRC diet recommendations cannot "be regarded as offering a cancer-free life,'' Grobstein points out. "But the weight of evidence in favor of preventative measures is Bowing--Cancer is not as inevita- e as death and taxes." Eating disorders linked to hormone imbalances To endocrinologists, the axiom isn't: "You are what you eat," but rather: "You are how much you eat" At least that is the impression one gets from research findings on the hormonal effects of disordered nutrition de scribed at the 65th annual meeting of the Endocrine Society held recently in San Francisco. That research focused on the en docrine systems of people who se verely overeat or undereat. It turns out, perhaps not surprisingly, that both obesity and anorexia nervosa-- the clinical name for what amounts to self-imposed starvation--are associ ated with significant changes in the body's hormone balances. Barnett Zumoff, a physician at Beth Israel Hospital in New York City, described research on the sys tem of reproductive hormones in obese women and men. Such studies, Zumoff says, "have revealed multiple abnormalities in the levels of pitu itary, ovarian, and testicular hor mones." The abnormalities, he says, "are strikingly different in men and women; endocrinologically, obesity is virtually two different diseases in the two sexes." According to Zumoff, research on the endocrine effects of obesity began because of clinical observations that suggest that obese men and women suffer impaired reproductive func tion. However, he says, such conclu sions are somewhat shaky: For men, the reference is a 1926 paper that virtually no subsequent data support; and for women, an unrelated dis ease--polycystic ovary syndrome-- which does affect reproductive func tion, likely accounts for the clinical observations. Nevertheless, research has revealed hormonal irregularities in the obese. It has been known for some time that women retain intravenously admin- istered estradiol (one of the family of estrogen molecules) in proportion to the degree of their obesity, Zumoff says. Recent research in Zumoffs laboratory has shown, however, that men do not exhibit this effect, a sex difference that Zumoff calls surpris ing. Zumoff suggests that women may have considerably more estrogen re ceptors in their adipose tissue than men, which, if true, could act to am plify the effects of estrogens in women. In obese women the ratio of folli cle-stimulating hormone (FSH) to luteinizing hormone (LH), both of which are produced in the pituitary gland, is elevated. This is caused, primarily, by a decrease in LH levels, Zumoff says. What makes this inter esting, he says, is that studies in monkeys on the effects of the fre quency of pulses of externally sup plied gonadotropic releasing hormone (GnRH), which is produced, naturally in the hypothalamus, had similar ef fects. In monkeys, the hypothalamus normally releases pulses of GnRH about once per hour. When the rate of pulse is decreased to once every 1.5 to 3 hours, the FSH/LH ratio increases because of a resultant decrease in pi tuitary release of LH. Zumoff suggests that obese women may have a similar slowing of the rate of hypo thalamic GnRH pulsing. He points out that premenopausal breast cancer patients demonstrate a similar hor mone imbalance and that obesity is a risk factor for breast cancer. He 3sets that slow GnRH pulsing t be the link between the two observations. Many researchers have demon strated that the male hormone, tes tosterone, is suppressed in the blood of obese men, Zumoff says. He stud ied testosterone levels in men who were from 10% below to 336% above normal weight and found that this suppression is proportional to the degree of obesity. Zumoffs research also suggests that the decrease in total testosterone concentration is ac companied by a decrease in the con centration of free testosterone, which is the fraction that is physiologically important. However, the low testos terone levels do not seem to have clinical consequences. Zumoff and his coworkers investigated three mea sures of sexual function in obese subjects: spermatogenesis by deter mination of sperm counts and sperm motility; libido, by structured psy chiatric interviews; and potency. All were normal in obese men. According to Zumoff, the probable cause of the low testosterone levels in obese men is increased conversion of androgens to estrogens in the adrenal gland. The increased estrogen levels act by a negative feedback mecha nism on the pituitary to suppress the secretion of FSH, and this in turn suppresses testicular production- of testosterone. This scenario is sup ported by the experimental observa tion that the drug dexamethasone, which suppresses adrenal gland ac tivity, reverses the testosterone ab normality, Zumoff says. Anorexia nervosa was the subject of two, separate papers at the meeting. Both Michelle P. Warren, a physician at Roosevelt Hospital in New York City, and Jack L. Katz, a psychiatrist at Montefiore Medical Center and Albert Einstein College of Medicine, also in New York City, pointed out the unique aspects of the condition: It occurs almost exclusively in women, it develops in the midadolescent years, and it invariably involves amenorrhea, or the absence of menstruation. (Katz noted that the few cases of anorexia nervosa in males generally occurred in early adolescent boys who also displaced other signif icant psychological disorders.) The hormonal disorders in an orexia nervosa, Warren and Katz point out, apparently have the hy pothalamus as their source. Accord ing to Katz, a study of more than 30 women emaciated from anorexia nervosa showed that all displayed immature patterns of LH secretion from the pituitary even though all were biologically adult. Pituitary re lease of LH and FSH is controlled by hypothalamic release of GnRH. In other studies, Warren says, when a severely ill anorectic is given GnRH, her pituitary response is that of a prepubescent female. Ifa woman with anorexia nervosa is given pulses of GnRH intravenously, the adult pat- 2S CAEN June 28.1962 s e h d h y e & ie n 11 e Q .f d .8 le n >f i* >- rf ys' n k it d a 'r it i: n l- y <e s it f- i- tz y- d10 ia i i >n ill e- y [n a d, a i of t- r tern of FSH and LH response even tually resumes, as does ovulation and menstruation. The amenorrhea, therefore, apparently results from the erepubescent hormonal pattern. infortunately, such GnRH admin istration does not change eating be havior and is, therefore, not a treat ment for the disorder. The question, Katz points out, is whether the hypothalamic disorder causes anorexia nervosa or is a symptom of the seriously disturbed pattern of eating and the emaciation that results from it. That answer isn't clear, but the evidence seems to in dicate that it is a symptom rather than a cause, at least initially. Because the hypothalamus is im portant in regulating food intake, Katz suggests, once its function is disrupts, for whatever reason, it may continue to disrupt eating behavior. "The situation would thus very much resemble an addiction," he says, "where, regardless of whatever paychodynamic forces put the addiction into motion, eventually the physio logical consequences take on a life of their own ana the syndrome becomes virtually independent of the causes." Warren and Katz suggest that an orexia nervosa may be the extreme in a continuum of endocrine abnor malities in women. For example, bu limia, in which young women ingest large numbers of calories and then induce vomiting, may not involve weight loss, but it does involve many of the hormonal abnormalities found in anorexia nervosa. Studies of women who are long-distance runners show that amenorrhea Is relatively common amongthem. They also dis play some of the same hormone ab normalities, but their abnormalities are completely reversible. Warren points out that the hor monal irregularities involved with poor nutrition and/or heavy exercise may have evolved as a form ofnatural birth control. A study of birth rates among women of the Bushmen tribe reveals that by far the maximum birth peak occurs nine months after weight is at a mHTiimim which, in turn, is controlled almost completely by fluctuations in food supply in the Kalahari Desert where they live. "Thus, a seasonal suppression of ov ulation appears to occur in these women," she says, "at a time when they are most active and weigh leas. In contrast to starvation, [this condition] is readily reversible and may act aa a mechanism of natural fertility con trol. Rudy Bourn, Son Francisco t Z or E lactone? O 0 0W_ =! // o Spectroscopy won't tell you. X-ray crystallography will. In less than a dayl Ifyou've heard that X-ray crystallography is complicated, time-consuming and costly, forget It Times have changed. Modern-day X-ray aystalioinstruments from t use automatic, computerized procedures to eliminate al of the time-consuming, intricate steps previously encountered in structure determinations. ' toucan get crystal-dear results In as Bttie as a day--not three months. Why X-ray crystaiography? Because it can prmride data that no other technique can. Jft now an essential, routine tool for the wd-iounded laboratory. 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