If it is true that women cry more than men, there could be abiological explanation. It is linked to an elaborate hormonalmechanism that USC researchers believe may also be responsible fordry eye - another condition more common in women than men.

Tears, which serve the purpose of keeping the eyes moist and healthy,are mainly produced by the lacrimal glands. When these glandsmalfunction, the resulting symptoms can range from mild irritation -including contact lens discomfort - to intense pain and burningsensations, blurred vision and sight-threatening corneal infectionsand ulcerations.

Dry eye conditions affect more than 10 million women in the UnitedStates, most frequently at times of hormonal alteration - such asduring pregnancy and lactation, after menstruation and as a result oforal contraceptive use. Some women also experience dry eye duringtheir monthly cycle, due to the rise and fall of sex hormone levels.In addition, women are more prone to develop a condition calledSjoegren's syndrome, an autoimmune disease that can destroy thelacrimal glands.

Using an animal model, researchers from the School of Medicine andthe Doheny Eye Institute have shown that, ironically, the crucialhormones controlling lacrimal gland function are testosterone andother male sex hormones called androgens. Women normally producethese hormones in small amounts, but when their testosterone levelsdrop below the already low norms, the lacrimal glands decrease insize and function.

"Low levels of available androgens in women are the commondenominator in most physiological states associated with dry eye,"said graduate student Ana Maria Azzarolo, the study's lead author.

The study, which was funded by the National Eye Intitute - a divisionof the National Institutes of Health - also indicates that thehormone prolactin may interact with testosterone to affect lacrimalgland function. Prolactin, which helps initiate and maintainlactation, is primarily produced in the pituitary gland, thoughlacrimal glands also produce the hormone. Not surprisingly, prolactinlevels are almost twice as high in females as in males.

"There are many distinct structural and biochemical differencesbetween lacrimal glands in men and women," said the study's seniorauthor, Dwight W. Warren, a professor of cell and neurobiology. "Webelieve that these differences are determined by the relative amountsof testosterone and prolactin."

To underscore this hormonal link, researchers in an earlier studygave testosterone to castrated male rats and to female rats. Theresult in both cases was male-like characteristics in the lacrimalglands.

"But other research also shows that these changes occur only if thepituitary, the main source of prolactin, is functioning - indicatingthat prolactin is interacting with a factor or factors produced bythe pituitary," Warren said.

In the USC study, scientists removed the pituitary glands from femalerats. The lacrimal glands soon began to atrophy, shrinking to halftheir original size, which in turn reduced the molecular machinerythat produces tears. Five days after the surgery, the rats receivedvarious high- and low-dose combinations of dihydrotestosterone (DHT),a form of testosterone, and prolactin. The treatment at leastpartially reversed most of the lacrimal gland changes.

"On the other hand, excessive prolactin also impairs lacrimal glandfunction," said Warren. "This may be why so many women experience dryeye problems during lactation."

But not all prolactin functions are necessarily tied to pituitaryfunctions. For example, prolactin independently controls thesynthesis of neurotransmitter receptors in the lacrimal glands. Thesereceptors determine the gland's ability to respond to nervestimulation and produce tears. Females have twice as many suchreceptors as males.

The USC research may also give clues to the autoimmune processresponsible for Sjoegren's syndrome. Sjoegren's, which is estimatedto afflict 2 million American women, appears to result from aproliferation of immune responses that begin in the lacrimal as wellas the salivary glands, which in many ways resemble the lacrimalgland. The disease's complications include dry mouth, vaginaldryness, muscle ache and fatigue, cerebral lesions resembling theplaques seen in multiple-sclerosis patients and an increasedincidence of non-Hodgkin's lymphoma.

"Together with the results of a study we published last October,these data suggest a pathway that leads from decreases oftestosterone and atrophy of the lacrimal glands to biochemicalchanges in the remaining lacrimal tissue," said Austin Mircheff,professor of physiology and biophysics and co-author of the study.

These biochemical changes include the production of certainmolecules, called histocompatibility antigens, known for theirimportance in organ transplant rejection. The histocompatibilityantigens cause the lacrimal tissue to actively provoke an immuneresponse against itself, ultimately destroying the gland, propagatingto other organs and causing the debilitating, chronic symptomsassociated with Sjoegren's.

Besides Sjoegren's syndrome, autoimmune diseases include multiplesclerosis; Type I (insulin-dependent or juvenile) diabetes;rheumatoid arthritis; ankylosing spondylitis, a form of rheumatoidarthritis; Grave's and Hashimoto's thyroid diseases; systemic lupuserythematosus; interstitial cystitis, a kind of bladder inflammation;and primary biliary cirrhosis, a chronic inflammation of the liver.

"Not all of these diseases may be related to inadequate androgenlevels, but they all may involve essentially the same mechanisms asthose triggered in the lacrimal glands when androgens decrease belownecessary values and initiate an immune response," Mircheff said.