GONADAL SEX-HORMONES AND DYSTONIA - EXPERIMENTAL STUDIES IN GENETICALLY DYSTONIC HAMSTERS

In some kinds of idiopathic dystonia, including paroxysmal dystonia, a role of sex hormones has been suggested because of female predominanc e and onset, recurrence, or exacerbation of dystonic symptoms with pre gnancy. Similar effects of pregnancy have recently been reported in a model of paroxysmal dystonia, the genetically dystonic hamster. Dyston ia in mutant hamsters of both genders is transient, i.e., exhibits spo ntaneous remission at around puberty, strongly suggesting involvement of gonadal sex hormones. For exploration of the role of sex hormones i n dystonia, we undertook a series of ontogenetic experiments in male a nd female dystonic hamsters. Mutant animals of both genders exhibited the same postnatal development of dystonia with maximum severity of dy stonic attacks between weaning and similar to 40 days of age and spont aneous remission thereafter. As shown by plasma sex hormone determinat ions and, in females, vaginal cytology, spontaneous improvement of the movement disorder coincided with puberty in both genders. Male and fe male hamsters had about the same plasma levels of progesterone. Compar ed with nondystonic hamsters, onset of puberty was significantly retar ded in both male and female dystonic hamsters. Furthermore, body weigh t gain was lower in dystonic animals, indicating retarded postnatal de velopment. Gonadectomy at time of weaning did not after the age-depend ent development and remission of dystonia, suggesting that gonadal sex hormones are not critically involved in the disease in hamsters. We p ropose that transient paroxysmal dystonia in mutant hamsters is caused by postnatal retardation of brain development resulting in a temporar y impairment of brain functions with spontaneous remission independent of gonadal sex hormones. In view of the fact that the brain can synth esize steroids such as progesterone independent of peripheral glands i n both genders, such neurosteroids might be involved in the postnatal brain maturation that leads to remission of dystonia at around puberty in mutant hamsters.