Robert C. Sergott

Recognition of Gonadotroph Adenomas in Women

BACKGROUNDnPituitary adenomas that arise from the gonadotroph cells are being recognized with increasing frequency in men, but they are still rarely recognized in women. This rarity could be the result of an actual difference in occurrence or of greater difficulty in recognition. The tumors are usually recognized in men more than 50 years old, but elevated serum gonadotropin levels in women of that age could be produced by normal gonadotroph cells.nnnMETHODSnBecause the stimulation of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and the beta subunit of LH (LH beta) by thyrotropin-releasing hormone (TRH) is a characteristic of gonadotroph adenomas in men, we administered TRH to 16 women with apparently nonsecreting pituitary macroadenomas and measured serum FSH, LH, LH beta, and the glycoprotein hormone alpha subunit every 15 minutes for 90 minutes before and 90 minutes after. The results were compared with the responses in 16 healthy women matched for age and in 10 women with macroadenomas secreting prolactin, growth hormone, or corticotropin. The tumors from 12 of the women with nonsecreting adenomas were cultured, and the secretion of FSH, LH, and LH beta in culture was determined.nnnRESULTSnEleven of the 16 women with apparently nonsecreting adenomas had significant increases in serum LH beta in response to TRH, 3 had FSH responses, and 4 had LH responses. None of the 16 healthy women and none of the 10 women with secreting macroadenomas had LH beta, FSH, or LH responses to TRH. Ten of the 12 adenomas that were cultured secreted readily detectable amounts of FSH, LH, and LH beta, and their secretion in vitro correlated with the patients responses to TRH in vivo.nnnCONCLUSIONSnMost apparently nonsecreting pituitary macroadenomas in women arise from gonadotroph cells. The majority of these can be recognized, even in postmenopausal women, by the serum LH beta responses to TRH, and some can be recognized by the responses of serum FSH and LH.

Antigalactocerebroside serum demyelinates optic nerve in vivo

Antiserum to the myelin lipid galactocerebroside (GalC) causes rapidly progressive focal demyelination when injected into guinea pig optic nerves. The capacity of anti-GalC to induce central nervous system demyelination is complement-dependent, and demyelinating activity is present in the immunoglobulin fraction of anti-GalC serum. Demyelination appears to result from primary damage to oligodendrocytes.

Positron Emission Tomography to Study the Effect of Eye Closure and Optic Nerve Damage on Human Cerebral Glucose Metabolism

We used 18F-2-fluoro-2-deoxyglucose and positron emission tomography to evaluate the effect of visual deprivation on brain glucose metabolism. In experiment 1, we compared local cerebral metabolic rates for glucose in seven normal volunteers studied with eyes closed to 11 age- and sex-matched normal volunteers studied with eyes open. Whole brain metabolism was similar in the two groups, and region/whole brain analysis of metabolic data showed that metabolism in the calcarine posterior cortex was decreased by 14% (P less than .05) with eye closure. Glucose metabolism in other regions was not different between the two groups. In experiment 2, we compared glucose metabolism in six patients with severe bilateral optic neuropathies to 12 age- and sex-matched normal controls. Whole brain glucose metabolism was unchanged in the optic neuropathy group compared to controls. However, statistically significant reductions in glucose metabolism in the optic neuropathy group were found in anterior calcarine cortex (17%), posterior calcarine cortex (27%), peristriate cortex (27%), and lateral occipital cortex (15%). The metabolic effects of damage to the pregeniculate visual system went well beyond those of simple eye closure.

Plaque Causing Homonymous Hemianopsia in Multiple Sclerosis Identified by Computed Tomography

Three patients with multiple sclerosis (women 20, 24, and 30 years old) had demyelinative plaques that produced homonymous hemianopsia. These lesions were identified by computed tomography which showed the plaques as hypodense areas. All patients with homonymous hemianopsia should undergo computed tomography; if a hypodense or enhancing lesion is identified, the diagnosis of multiple sclerosis must be considered.

Current concepts of the pathogenesis of optic neuritis associated with multiple sclerosis

Optic neuritis may occur as an isolated entity or as a manifestation of multiple sclerosis (MS), a widespread central nervous system demyelinating disease. Clinical, electrophysiological, magnetic resonance imaging and neuropathologic data support the hypothesis that idiopathic optic neuritis represents a restricted form of MS. The current evidence for viral, cell mediated, and antibody-induced etiologies of MS and optic neuritis are reviewed.

Mammalian Reovirus Receptor Expression by Oligodendrocytes

A serotype-specific cell surface receptor for the mammalian reovirus type 3 is defined by the mouse monoclonal anti-receptor antibody 87.92.6 and the xenogeneic rabbit antiserum anti-ID3,* both directed against an idiotope of the 9B.G5 anti-reovirus type 3 hemagglutinin antibody. The reovirus receptor and the &adrenergic receptor have similar tissue distributions and biochemical features. However, the catecholamine and virus binding sites appear to be distinct. Whereas the binding of beta agonists typically leads to activation of adenylate cyclase and the accumulation of intracellular cyclic AMP, the binding of intact reovirus type 3, purified hemagglutinin, and anti-reovirus receptor antibodies inhibit DNA synthesis and cell growth of mouse L fibroblasts, mouse R1.l thymoma cells, and rat B104 neuroblastoma cells (reference 4 and unpublished data). Recent studies demonstrated that immunoreactive reovirus receptor is expressed by mature oligodendrocytes and both type 1 and type 2 astrocytes.5 The present studies were undertaken to determine the timing and cellular specificity of expression of immunoreactive reovirus receptor during glial development and to determine the effects of antibody binding on oligodendrocytes or myelin in vivo.

In vivo Modulation of Oligodendrocyte Function by an Anti-Receptor Antibody

The receptor for reovirus serotype 3 (Reo3R) is biochemically, pharmacologically, and antigenically related to the adrenergic receptors. Previous studies have demonstrated that anti-Reo3R antibodies and Reo3R-binding peptides alter oligodendrocyte differentiation in culture. In the present studies, antibodies and peptides that bind the Reo3R were found to alter myelin morphology in vivo. Microinjection of purified anti-Reo3R antibody into guinea pig optic nerves produced expansion of the adaxonal oligodendrocyte cytoplasm, separation of myelin lamellae, widening of Schmidt-Lanterman clefts, myelin vesiculation, and demyelination. A divalent Reo3R-binding peptide reproduced some of these changes. Anti-Reo3R antibodies and Reo3R-binding peptides alter oligodendrocyte function in vivo resulting in myelin changes. These effects appear to be mediated directly by Reo3R perturbation, at least in part, rather than through activation of additional effector mechanisms.