Neuronal hypertrophy in the hypothalamus of older men

A striking neuronal hypertrophy occurs in the infundibular nucleus of postmenopausal women. To determine the gender specificity of this response, we measured the areas of neuronal profiles in the infundibular nucleus of young (21, 32, and 41 years) and older (60, 61, and 68 years) men and compared them to data reported previously from the hypothalami of pre-(28, 32, and 40 years) and postmenopausal women (58, 62, and 74 years). Sagittal blocks of formalin-fixed hypothalami were paraffin embedded, serially sectioned and stained with cresyl-violet. The profile areas of 2,429 infundibular neurons were manually digitized using an image-combining computer microscope. The contralateral hypothalamus of each subject was cryoprotected, frozen-sectioned in the coronal plane and also stained with cresyl violet. The infundibular nuclear volume and the total number of neurons were estimated from the coronal sections using stereologica methods. The mean profile area of infundibular neurons from older men (176.6 ± μm²) was significantly larger than that of young men (147.0 ± 1.3 μm²). There was also a significant increase in the density of hypertrophied neurons (>226 μm² profile area) in the infundibular nucleus of older men. There was no difference in infundibular nuclear volume or total number of infundibular neurons between the young and older men. However, the volume of infundibular nucleus associated with an average neuron was significantly increased in the older men. A comparison previous data obtained from pre- and postmenopausal women revealed that the profile area of infundibular neurons was equal in young men and young women. However, the profile area of neurons in the postmenopausal women (190.4 ± 2.1 μm²) was significantly greater than that of older men. Furthermore, there was more than a threefold increase in the density of hypertrophied cells in the postmenopausal group compared to the older men. We have previously hypothesized that neuronal hypertrophy in the infundibular nucleus of older women is secondary to the loss of steroid negative feedback. The moderate hypertrophy of infundibular neurons in older men may be due to the reduced circulating testosterone levels in this age group.