Jonathan M. Lloyd

Neuroendocrine concomitants of reproductive aging

Depletion of ovarian follicles is often thought to be the determining factor in female reproductive aging. However, increasing evidence suggests that neural and neuroendocrine changes play important causative roles in the decline of regular reproductive cycles leading to the menopause. A blunting or suppression in the daily pattern of secretion of several neuroendocrine hormones has been documented in aging laboratory animals and humans. Investigators have designed experiments to test whether these changes reflect multiple unrelated changes in the regulation of each of these hormones, or whether these alterations result from a fundamental change in the time-keeping mechanism that underlie these patterns of hormone secretion. Oscillations that occur approximately every 24 h are a hallmark of most living organisms. These cycles provide the organism with the capability of coordinating events that occur at higher (hourly) and lower (weekly or monthly) frequencies within an individual organism, and with the capability of synchronizing these events with the external environment. In mammals, the hypothalamic suprachiasmatic nucleus is thought to be a master oscillator that regulates most circadian rhythms in mammals. Perturbations in temporal organization occur during aging and influence multiple physiological systems, including reproductive cyclicity in females. Thus, the question for neuroendocrinologists is: Do changes in the cyclic pattern of hormone secretion reflect a change in the master oscillator, and do these changes play a role in female reproductive aging? Data from our laboratory demonstrate that the timing of the preovulatory and steroid-induced luteinizing hormone (LH) surge changes during middle-age in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Age-Related Changes in Opiate Receptor Densities in Discrete Hypothalamic Nuclei of Ovariectomized (OVX) and Estradiol (E2)-Treated Rats.

Hypothalamic opioid peptides influence a variety of diverse functions. During the aging process many aspects of hypothalamic opioid activity appear to change. Previously, we reported in young rats that steroid-induced changes in the density of naloxone binding sites parallel altered responsiveness to opiates. To determine whether age-related changes in opiate function are associated with alterations in the density of opiate receptors, we measured the density of naloxone binding sites at various times of day in young, middle-aged, and old ovariectomized or ovariectomized, estradiol-treated rats. In the medial preoptic nucleus, there is no age-related decline in the density of naloxone binding sites in ovariectomized animals. In the arcuate and ventromedial nuclei, the density of naloxone binding sites declines by middle-age and is suppressed further in the old animals. In the median eminence, there is a similar progressive age-related decline in naloxone receptor densities. In young animals estradiol treatment suppresses naloxone binding sites in all four nuclei. The ability to respond to steroid treatment persists in middle-aged and old animals except in the median eminence. These data demonstrate that the density of naloxone binding sites and the ability of estradiol to induce changes in these binding sites changes with age. The rate of these progressive changes is different in each brain region and correlates with age-related changes in opiate-mediated functions.

Assessment of Proopiomelanocortin Gene Expression in Brain

Publisher Summary This chapter discusses the assessment of proopiomelanocortin gene expression in brain. In situ hybridization methodology can be divided into three basic steps: (1) preparation of tissue, (2) hybridization with a specific mRNA in tissue, and (3) quantization of the hybridization signal. Which steps are more important depend partially on the questions posed by the investigator. Thus, if one wishes to assess the morphology of cells expression of a gene of interest, the histological techniques used in preparation of the tissue become paramount. On the other hand, if one wishes to identify the anatomical distribution within the tissue of the cells that express a gene of interest, then steps must be taken to optimize sensitivity of the assay to ensure that cells that express low levels of the gene are detectable. If one wishes to compare levels of gene expression under different physiological or pharmacological conditions, it is essential to optimize hybridization and quantization to allow relative differences between groups to be detectable and reliable.