Medication status and polycystic ovary syndrome in women with bipolar disorder: a preliminary report.

BACKGROUND: In patients with epilepsy, polycystic ovary (PCO) syndrome has been reported to be associated with the use of the anticonvulsant divalproex sodium. Whether PCO syndrome is associated with divalproex use in patients with bipolar disorder has not previously been explored. METHOD: Twenty-two female outpatients with a DSM-IV diagnosis of bipolar disorder who were between the ages of 18 and 45 years (inclusive) and who were taking lithium and/or divalproex (10, divalproex monotherapy; 10, lithium monotherapy; 2, divalproex/lithium combination therapy) were evaluated. Patients completed questionnaires about their medical, psychiatric, and reproductive health histories, and body mass indices were calculated. In the early follicular phase of their menstrual cycle, women were examined for hirsutism, given a pelvic ultrasound, and/or assessed for changes in laboratory values such as serum levels of testosterone, free testosterone, estradiol, estrone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, luteinizing hormone, follicle-stimulating hormone, and 17-OH progesterone. RESULTS: All 10 patients on lithium monotherapy, 6 of 10 patients on divalproex monotherapy, and both of the patients on divalproex/lithium combination therapy reported some type of menstrual dysfunction, which, in 4 cases, had preceded the diagnosis of bipolar disorder. Hirsutism was not common in any group, but obesity was prominent in all groups. Ovarian ultrasound revealed an increased number of ovarian follicles in 1 patient taking lithium and in none of the patients taking divalproex. Hormonal screening did not indicate PCO-like changes in any patient. CONCLUSION: In this pilot study of bipolar patients, PCO-like changes were not seen in women receiving divalproex or lithium. However, independent of therapeutic agent used, the bipolar women in this study reported high rates of menstrual disturbances, suggesting that the hypothalamic-pituitary-gonadal axis may be compromised in some women with bipolar disorder.

Release from live choroid plexus of apical fragments and electrophoretic characterization of their synthetic products.

Protein synthesis and secretion by the choroid plexus (CP) has been implicated as a major source of certain proteins in cerebrospinal fluid (CSF), such as transthyretin. The suggestion that proteins are elaborated from CP through apocrine secretion has been borne out by the presence of newly labeled proteins in apical protrusions from CP (Agnew et al.: Cell and Tissue Research 208:261-281, 1980a). When the protrusions (aposomes) separate from the cells, they continue to incorporate labeled amino acids (Gudeman et al.: Tissue and Cell 19:101-109, 1987). In the present work the formation of aposomes in live CP explants indicated that these spheroids were not the result of fixation. Aposomes were also identified within rat CSF by immunohistochemistry with monoclonal directed against aposomes as well as with anti-transthyretin serum. The protein product of aposomes was characterized by 2-dimensional SDS-PAGE and compared to the protein products of whole CP tissue. Paradoxically, transthyretin, a heavily labeled protein in the tissue, was virtually undetected in the aposome synthetic profile. However, four other proteins were expressed in relatively equivalent amounts by the aposomes. The presence of mRNA in aposomes was detected with a poly dT probe, and the presence of actin was revealed by phalloidin staining of aposomes. These studies provide a more comprehensive definition of aposomes, but the functions of their secreted proteins remains to be determined.

Protein secretion by choroid plexus: isolated apical fragments synthesize protein in vitro.

Protein synthesis was studied in the isolated rat choroid plexus. When the choroid plexus was studied by transmission electron microscopy, membrane-bound structures were often observed in the ventricular space. These structures appear to bud from the apical surface of the epithelial cells. In the present study, we attempted to isolate these membrane-bound cellular fragments from the choroid plexus and to determine their ability to synthesize proteins. The apical fragments (aposomes) were isolated from the choroid plexus by allowing tissue explants to incubate in media (37 degrees C) for 1 h. The tissue was removed and the media, now containing aposomes, was incubated with [S35]methionine (100 microCi). The media was collected and analysed by SDS-PAGE followed by fluorography. Parallel [S35]methionine incubations were done with whole tissue explants. The SDS-PAGE protein derived from the aposomes was similar to the profile derived from the tissue. In addition, proteins detected in CSF had relative molecular weights comparable to the products synthesized by aposomes. These observations suggest that aposomes provide an additional route of entry for proteins into CSF.