Ontogenesis of Growth Hormone-Releasing Hormone Neurons in the Rat Hypothalamus

Goda

Journal of Endocrinology

et al. 2005

In order to study GH cell differentiation, we used the clonal cell lines called MtT/E and MtT/S cells, which were derived from a rat mammotrophic pituitary tumor. Although MtT/E cells are non-hormone-producing ones, Pit-1 protein is present in their nuclei, which suggests that MtT/E cells are progenitor cells of the Pit-1 cell lineage and have the potential to differentiate into hormoneproducing cells. On the other hand, MtT/S cells produce GH; however, the responsiveness to GH-releasing hormone (GHRH) is weak and only a small number of secretory granules are present in their cytoplasm, which suggests that MtT/S cells are premature GH cells. In order to differentiate into GH cells from MtT/E cells as a progenitor cell, we examined several differentiation factors and found that retinoic acid (RA) induced the differentiation of MtT/E cells into GH-producing cells. RAinduced GH cells partially matured with the glucocorticoid treatment; however, the responsiveness to GHRH on GH secretion was incomplete. In order to elucidate the mechanism underlying full differentiation of GH cells, we used MtT/S cells. We treated MtT/S cells with glucocorticoid and found that they differentiated into mature GH cells with many secretory granules in their cytoplasm and they responded well to GHRH. These results suggested that MtT/E and MtT/S cells are progenitor or premature GH cells, and show different responses to differentiation factors. Our data also suggested that GH cells differentiate from their progenitor cells through multistep processes.

Section: Discussionsupporting

confidence: 61%

Multistep differentiation of GH-producing cells from their immature cells

Goda

Journal of Endocrinology

et al. 2005

“…The ontogeny of neuropeptide gene expression in the Arcuate nucleus (Arc) is critical for the neuroendocrine control of feeding, metabolism, and reproduction [19][20][21][22][23][24][25][26][27][28][29]. In adult rats, GALP is expressed in the Arc of the hypothalamus and GALP gene expression is regulated by leptin, insulin, and metabolic fuels [6,30,31].…”

Section: Discussionmentioning

confidence: 99%

Sex differences in the effect of prepubertal GALP infusion on growth, metabolism and LH secretion

Rich

Reyes

Reap

et al. 2007

Physiology & Behavior

Sex differences in the effect of prepubertal GALP infusion on growth, metabolism and LH secretion, Physiol. Behav. XX(XX): XXX. The hypothalamic neuropeptide, galanin-like peptide (GALP), is known to have an effect on energy expenditure and reproduction in adult male rats, but little work has been done on prepubertal rats. We hypothesized that hypothalamic GALP is involved in physiological changes associated with the onset of puberty. To test this hypothesis, we first determined the postnatal ontogeny of GALP gene expression via in situ hybridization of developing male and female rat pups through adulthood. GALP gene expression was not observed in either male or female rat pups until after postnatal day (PND) 10 and did not reach adult-like levels until after weaning (PND25). To determine if exogenous GALP could induce the onset of puberty, PND25 male and female rats were implanted with lateral ventricular cannulas connected to an osmotic minipump that delivered either GALP or vehicle. GALP infusion significantly (p < 0.05) increased body weight, food intake, and metabolic rate in male but not female rats compared to control infusion. After two weeks, GALP infusion had no significant effect on the onset of puberty, percent body fat, nor plasma levels of insulin, FSH or gonadal steroids in either sex; however, GALP did significantly (p < 0.05) increase plasma levels of LH and leptin in male but not female rats and increased plasma growth hormone (GH) in both sexes. Our observations further demonstrate a sex difference in GALP responsiveness in prepubertal rats. These data suggest that GALP may be involved with the prepubertal increase in circulating leptin, LH, and GH resulting in an increase in metabolic rate and lean growth associated with puberty.

“…Immunoreactive GHRH was reported as first detectable in median eminence at e18 [25]to e20 [26], and perikarya were visualized in arcuate nucleus on e19.5 [25], or on the day of birth [26, 27]. In two of these studies [25, 27], the pups were treated for 24 h with intracerebroventricular colchicine to block axonal transport. Greater than 50% of the treated animals do not survive the use of colchicine either as fetuses [25]or before 14 days of age [Personal observations].…”

Section: Discussionmentioning

confidence: 99%

Growth Hormone Releasing Hormone Expression During Postnatal Development in Growth Hormone-Deficient Ames Dwarf Mice:mRNA in situ Hybridization

1998

Several genetic mutations in mice and rats that produce lifelong growth hormone (GH) deficiency result in overexpression of GH-releasing hormone (GHRH) mRNA in hypothalamic arcuate nucleus neurons. In order to examine the development of this condition, GHRH mRNA expression was quantified in Ames dwarf (df/df) and normal (DF/?) mice at 1 (day of birth), 3, 7, 14, 21 and 60 postnatal days (d) following in situ hybridization. Total mRNA was assessed using computer-assisted densitometry after X-ray film autoradiography, and mRNA expression per neuron was quantified by counts of grains per cell after emulsion autoradiography. Total GHRH mRNA was the same in dwarf and normal mice at 1, 3 and 7d. GHRH mRNA in dwarfs increased at 14d to 240% of that in DF/? (p < 0.005); the percentage overexpression in dwarf mice remained ≧200% through 60d, although total GHRH mRNA increased in both dwarfs and normals during this period. GHRH mRNA per neuron was the same in normal and dwarf mice at 1d, then increased in dwarfs to 190% of that in normals at 3d (p < 0.05), and rose to 300% of normal levels by 7d and beyond (p < 0.005). There was no sexual dimorphism in expression by either measure in normal or dwarf mice. These results indicate that an increase in GHRH mRNA in Ames dwarf mice is first detectable at 3d, a period of approximately 7d after the failure to initiate GH production, which occurs normally at embryonic day 17.5. The onset of GHRH overexpression occurs earlier than the decline of either hypophysiotropic somatostatin or dopamine in Ames dwarf mice. This difference may be due to the stimulatory action of GHRH, as opposed to the inhibitory effects of factors examined previously.