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T Dellovade

Publications and source records attributed to T Dellovade.

6 recordsLinked to original sources
PubMed1998

Aspects of GnRH neurobiology conserved across vertebrate forms.

The decapeptide gonadotropin-releasing hormone (GnRH) came into prominence because of its roles in releasing luteinizing hormone and follicle-stimulating hormone and promoting reproductive behavior. At least three aspects of GnRH neurobiology have features which may be universal among vertebrates. First, the GnRH neuronal migration from the olfactory placode into the basal forebrain appears to hold true for forms ranging from fish to humans. Second, for proper agonist activity in the anterior pituitary, GnRH must be released in a pulsatile fashion. Since GT-1 neuronal cell cultures can demonstrate pulsatile release, it must be concluded that GnRH neuronal networks themselves can manage this type of pulsatility. Using a neuronal mathematical model with "minimalist" assumptions, we demonstrated that a network of identical neurons can achieve this self-organizing property without the use of, or spontaneous appearance of, "pacemaker cells." Indeed, since many parameter combinations worked, and since no information about species identity or chemical cell type is provided to the model, this conclusion could apply across many vertebrate forms and, perhaps, even for other neuroendocrine cell types. Third, Fernald and colleagues (this issue of General and Comparative Endocrinology) have demonstrated remarkable effects of social context on GnRH expression in fish. Reviewed here are some data in musk shrews suggesting that behavioral and social stimuli can also modify GnRH neurons in mammals. Therefore, although GnRH neuronal mechanisms are adapted to meet species-typical variations in environment and physiology, some of the important features of this system appear to be widely conserved.

Animals↗
PubMed1997

Glucocorticoid repression of gonadotropin-releasing hormone gene expression and secretion in morphologically distinct subpopulations of GT1-7 cells.

Two morphologically distinct subpopulations of GT1-7 cells have been characterized and examined for their responsiveness to glucocorticoids. Type I cells have a neuronal phenotype, extending many lengthy processes, and express neuronal, but not glial, markers. Type II cells show weaker or negative immunostaining for neuronal markers and exhibit fewer processes. The effect of glucocorticoids on gonadotropin-releasing hormone (GnRH) secretion and gene expression was compared in type I and type II GT1-7 cells. For secretion studies, cells were attached to Cytodex beads and perifused with control medium or medium containing dexamethasone (dex). The high level of GnRH secreted by type I cells was slightly enhanced in the presence of dex, whereas dex rapidly and profoundly decreased the already low level of GnRH secreted by type II cells. Immunocytochemistry for GnRH showed dark reaction product in the cell bodies and processes of type I cells and little or no immunoreactivity in type II cells. Both the endogenous mouse GnRH mRNA and the transcriptional activity of a mouse GnRH promoter luciferase reporter gene plasmid were suppressed to a greater extent in type II cells than in type I. In electrophoretic mobility shift assays, there was no difference between type I and type II nuclear extracts in the pattern of protein-DNA complexes formed on two previously identified negative glucocorticoid response elements located at -237 to -201 and -184 to -150 bp of the mouse promoter. Both cell types contained glucocorticoid receptors (GR) by Western blot analysis. Cytosols from type I or type II cells were incubated with [3H]dex to obtain GR binding parameters. Binding data were consistent with a one-site model for dex binding in each case. Small differences in Kd (1.7 nM, type I; 3.1 nM, type II) or Bmax (approximately 3600 sites/cell, type I; approximately 1800 sites/cell, type II) were not likely to account for the differential sensitivity to dex treatment. In conclusion, nuclear alterations in type II cells leading to greater transcriptional susceptibility to dex, coupled with low GnRH storage levels, may be reflected in exquisite sensitivity of GnRH secretion to glucocorticoid repression. This represents the first example of a steroid hormone acting directly on GnRH-producing cells to alter GnRH secretion.

Animals↗
PubMed1997

Gender-specific induction of pituitary RNA by estrogen and its modification by thyroid hormone.

Estrogen and thyroid hormones play important roles in the regulation of pituitary function. We presently show that pituitary weight and total cellular RNA levels were significantly decreased by ovariectomy in female rats and were significantly increased by castration in males, without alterations in pituitary DNA levels as compared to intact animals. Treatment with a single dose of estrogen produced a significant increase in pituitary RNA in ovariectomized females but not castrated males. This effect was more obvious following multiple doses of estrogen, and was blocked by pretreatment with cycloheximide, or surprisingly by concomitant administration of triiodothyronine (T3). Analysis of estrogen response element (ERE) binding activity in pituitary nuclear protein extracts revealed that estrogen produced a rapid induction of a slow mobility complex of ERE binding in ovariectomized females much greater than in castrated males. Thus, estrogen-induced increases in pituitary total RNA levels are dependent on new protein synthesis, are gender-specific, are inhibited by T3, and may be mediated via specific estrogen-induced changes in protein-DNA interactions.

Animals↗
PubMed1997

Differential LHRH secretion, dye coupling, and protein expression in two morphologically distinct cell types identified in GT1-7 cultures.

The immortalized neuronal cell line, GT1-7, has been shown to secrete LHRH in a pulsatile manner and to possess many other characteristics of hypothalamic LHRH neurons in vivo, and thus provides a potential model system for studying biochemical and physiological mechanisms regulating LHRH secretion. In the present study, two morphologically and functionally distinct types of cells have been identified in GT1-7 cultures and each type purified to over 95% homogeneity. One type (N cells) appeared more neuronal with extended neurites and somewhat rounded cell perikarya, while the other type (G cells) had flatter cell perikarya that contained filopodia but no neurites. Growth properties of the two cell types also differed. The doubling time for proliferation of N cells was nearly two-fold shorter than that for G cells and N cells displayed 'piling up' whereas G cells exhibited contact inhibition. Functionally, N cells, but not G cells, were dye-coupled as measured by a fluorescence photobleaching assay. While both cell types expressed LHRH, N cells released significantly higher levels of LHRH into the culture media and exhibited more intense LHRH immunostaining. The two cell types also showed differences in immunostaining for other proteins. N cells, unlike G cells, immunostained positive for neuron-specific enolase (NSE), whereas G cells, unlike N cells, stained immunopositive for vimentin. Both cell types expressed SV-40 T antigen protein, indicating that they were derived from the same transgenic mouse hypothalamic tumour. The physiological significance of these two cell types in GT1-7 cultures remains to be determined, but elucidation of their morphological and biochemical properties is intended to contribute to better understanding and application of this experimentally important neuroendocrine cell line.

Adenylyl Cyclases↗
PubMed1996

Hypothalamic cellular and molecular mechanisms helping to satisfy axiomatic requirements for reproduction.

In the absence of universal equations expressing neurobiological findings, the safest theoretical approach for the neuroendocrinologist is to start from axiomatic requirements for biologically adaptive neural mechanisms, in our case for reproduction. From this emerge two themes: the likely importance of interactions between internal (hormonal) and external signals in controlling gene expression relevant to reproductive functions; and, second, the vision of molecular interactions on DNA subserving environmental impacts on reproduction. The first theoretical notion has so far yielded data showing a role for synaptic inputs during the onset of estradiol actions for the hormone's induction of enkephalin mRNA, a finding which parallels earlier behavioral results. As well, noxious somatosensory inputs interact with estrogens and progesterone in their influence on enkephalin gene expression. The second theme led to novel investigations of thyroid influences on reproductive molecular biology and behavior, including the ability of exogenous or endogenous thyroid hormones to reduce female mating responses. Since elevated thyroid hormone levels could signal environmental cold, our experiments offer the possibility of explaining ethological facts at a molecular level. More generally, nuclear hormone receptor interactions on the surface of DNA may offer a new level of neural integration revealed first by hormone effects in neuroendocrine cells.

Animals↗