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 predominance and onset, recurrence, or exacerbation of dystonic symptoms with pregnancy. Similar effects of pregnancy have recently been reported in a model of paroxysmal dystonia, the genetically dystonic hamster. Dystonia in mutant hamsters of both genders is transient, i.e., exhibits spontaneous remission at around puberty, strongly suggesting involvement of gonadal sex hormones. For exploration of the role of sex hormones in dystonia, we undertook a series of ontogenetic experiments in male and female dystonic hamsters. Mutant animals of both genders exhibited the same postnatal development of dystonia with maximum severity of dystonic attacks between weaning and approximately 40 days of age and spontaneous remission thereafter. As shown by plasma sex hormone determinations and, in females, vaginal cytology, spontaneous improvement of the movement disorder coincided with puberty in both genders. Male and female hamsters had about the same plasma levels of progesterone. Compared with nondystonic hamsters, onset of puberty was significantly retarded in both male and female dystonic hamsters. Furthermore, body weight gain was lower in dystonic animals, indicating retarded postnatal development. Gonadectomy at time of weaning did not alter the age-dependent development and remission of dystonia, suggesting that gonadal sex hormones are not critically involved in the disease in hamsters. We propose that transient paroxysmal dystonia in mutant hamsters is caused by postnatal retardation of brain development resulting in a temporary impairment of brain functions with spontaneous remission independent of gonadal sex hormones. In view of the fact that the brain can synthesize steroids such as progesterone independent of peripheral glands in both genders, such neurosteroids might be involved in the postnatal brain maturation that leads to remission of dystonia at around puberty in mutant hamsters.