scholarly journals Postnatal Regression of Hypothalamic Dopaminergic Neurons in Prolactin-Deficient Snell Dwarf Mice

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5656-5664 ◽  
Author(s):  
C. J. Phelps
Keyword(s):  
Neuronal Development ◽  
Cell Number ◽  
Zona Incerta ◽  
Initial Increase ◽  
Neuron Number ◽  
Ames Dwarf ◽  
Snell Dwarf ◽  
Catecholamine Fluorescence ◽  
Dwarf Mice ◽  
D 23

Abstract Both Snell (Pit-1dw or dwj, dw/dw) and Ames (Prophet of Pit-1df, df/df) dwarf mice fail to produce prolactin (PRL) as well as GH due to deficient transcription factor Pit-1 activity and have reduced numbers of hypothalamic PRL-inhibiting area A12 tuberoinfundibular dopaminergic (TIDA) neurons. It has been reported that the TIDA deficit in Ames dwarf mice develops postnatally as a reduction in number after an initial increase that is comparable to that of normal siblings. The present study was designed to characterize A12 TIDA neuronal development in the Snell dwarf (dw/dw) compared with littermate normal mice. Brains of normal (DW/?) and dwj/dwj mice were examined at 7, 14, 21, 30, and ≥ 60 postnatal days (d) by catecholamine fluorescence and quantification of neuron number after tyrosine hydroxylase immunostaining in dopaminergic (DA) areas A12, A13 (medial zona incerta), and A14 (periventricular nucleus). Fluorescence was less in dw/dw than in DW/? A12 perikarya and median eminence but was not reduced in other DA areas, such as substantia nigra, at all ages; A12 fluorescence was virtually absent in Snell dwarf adults. Numbers of TIDA neurons were comparable in normal and Snell dwarf mice at 7 d. In normal (DW/?) mice, A12 neurons increased in number to adult levels at 14 d and were significantly higher than in Snell dwarf (dw/dw) mice at 14 d (P < 0.05) and at subsequent ages (P < 0.01). In Snell dwarf mice, numbers of A12 neurons did not differ at 7, 14, and 21 d, decreased at 30 d (P < 0.05), and reached, at 60 d, 23% of the population in normal sibling mice (P < 0.01 compared with earlier ages). Neuron numbers in nonhypophysiotropic DA area A13 did not vary with age or phenotype. In A14, cell number was higher in both phenotypes at 14 d (P < 0.05 for DW/?; P < 0.01 for dw/dw); neuron number was lower in dw/dw than in DW/? mice at 30 d (P < 0.05) and 60 d (P < 0.01). Thus, compared with normal mice of the same strain, the A12 deficit is more severe in Snell (dw/dw) than in Ames (df/df) dwarf hypothalamus (48% of DF/?), as previously reported, and develops as a decline from the population present at 7 d rather than first increasing. A reduction in A14 neuron number also occurs in the Snell dwarf. Treatment of DW/dw- and dw/dw-containing litters with ovine PRL (50 μg/d, ip), beginning at 12 or 7 d and continuing until 42 d, resulted in TIDA neuron numbers in Snell dwarfs that were lower than those in normal siblings (P < 0.01 for both) but were higher than in untreated adult dwarfs and comparable to the TIDA population size in dwarfs at 7 d, indicating that PRL maintained this maximal number and prevented TIDA neuron dedifferentiation, which occurs in dwarf postnatal development.

scholarly journals Long-Term, Homologous Prolactin, Administered through Ectopic Pituitary Grafts, Induces Hypothalamic Dopamine Neuron Differentiation in Adult Snell Dwarf Mice

Endocrinology ◽  
2007 ◽  
Vol 149 (4) ◽  
pp. 2010-2018 ◽  
Author(s):  
Christina E. Khodr ◽  
Sara M. Clark ◽  
David L. Hurley ◽  
Carol J. Phelps
Keyword(s):  
Third Ventricle ◽  
Zona Incerta ◽  
Neuron Population ◽  
Neuron Number ◽  
Early Postnatal Development ◽  
Snell Dwarf ◽  
Catecholamine Histofluorescence ◽  
Periventricular Area ◽  
Pituitary Prolactin ◽  
Dwarf Mice

Pituitary prolactin (PRL) secretion is inhibited by dopamine (DA) released into the portal circulation from hypothalamic tuberoinfundibular DA (TIDA) neurons. Ames (df/df) and Snell (dw/dw) dwarf mice lack PRL, GH, and TSH, abrogating feedback and resulting in a reduced hypophysiotropic TIDA population. In Ames df/df, ovine PRL administration for 30 d during early postnatal development increases the TIDA neuron number to normal, but 30 d PRL treatment of adult df/df does not. The present study investigated the effects of homologous PRL, administered via renal capsule pituitary graft surgery for 4 or 6 months, on hypothalamic DA neurons in adult Snell dw/dw mice using catecholamine histofluorescence, tyrosine hydroxylase immunocytochemistry, and bromodeoxyuridine immunocytochemistry. PRL treatment did not affect TIDA neuron number in normal mice, but 4- and 6-month PRL-treated dw/dw had significantly increased (P ≤ 0.01) TIDA (area A12) neurons compared with untreated dw/dw. Snell dwarfs treated with PRL for 6 months had more (P ≤ 0.01) TIDA neurons than 4-month PRL-treated dw/dw, but lower (P ≤ 0.01) numbers than normal mice. Periventricular nucleus (area A14) neuron number was lower in dwarfs than in normal mice, regardless of treatment. Zona incerta (area A13) neuron number was unchanged among phenotypes and treatments. Prolactin was unable to induce differentiation of a normal-sized A14 neuron population in dw/dw. Bromodeoxyuridine incorporation was lower (P ≤ 0.01) in 6-month PRL-treated normal mice than in 6-month PRL-treated dwarfs in the subventricular zone of the lateral ventricle and in the dentate gyrus, and lower (P ≤ 0.05) in 4-month untreated dwarfs than in 4-month untreated normal mice in the median eminence and the periventricular area surrounding the third ventricle. Thus, a PRL-sensitive TIDA neuron population exists in adult Snell dwarf mice when replacement uses homologous hormone and/or a longer duration. This finding indicates that there is potential for neuronal differentiation beyond early developmental periods and suggests plasticity within the mature hypothalamus.

Cellular growth in organs of dwarf mice during treatment with growth hormone, thyroxine and plasma fractions containing somatomedin activity

1982 ◽  
Vol 99 (1) ◽  
pp. 150-160 ◽  
Author(s):  
Sylvia van Buul-Offers ◽  
Jan Leo Van den Brande ◽  
L. Dumoleijn ◽  
M. Feijlbrief ◽  
C. M. Hoogerbrugge ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Human Growth ◽  
Cell Number ◽  
Small Degree ◽  
Cellular Growth ◽  
Nucleic Acid Metabolism ◽  
Plasma Fractions ◽  
Snell Dwarf ◽  
Division Cell ◽  
Dwarf Mice

Abstract. DNA, RNA and protein content of the liver, kidneys and spleen were studied in dwarf mice during treatment with human growth hormone (hGH), thyroxine and plasma fractions containing somatomedin activity (SM-P1 and SM-P4). This investigation has revealed that part of the growth of the liver and all growth of the spleen obtained with the administered preparations, are a consequence of nuclear division. Cell enlargement is not induced in the spleen by either of the preparations used. In the liver a small degree of hypertrophy is obtained with SM-P1. In the kidney both cell number and cell size are stimulated by thyroxine and to a lesser extent by hGH and SM-P1. With regards to the RNA content per cell an increase is obtained with hGH and thyroxine in the liver and in the kidneys also with SM-P1, but not in the spleen. These data demonstrate that semi-purified SM-preparations, like hGH and thyroxine, might be potent stimuli for the restoration of the impaired nucleic acid metabolism in these organs of the Snell dwarf mouse.

ANALYSIS OF GROWTH HORMONE GENES IN MICE WITH GENETIC DEFECTS OF GROWTH HORMONE EXPRESSION

1982 ◽  
Vol 92 (3) ◽  
pp. 405-407 ◽  
Author(s):  
J. A. PHILLIPS ◽  
W. G. BEAMER ◽  
A. BARTKE
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Genetic Disorders ◽  
Restriction Endonuclease Analysis ◽  
Genetic Defects ◽  
Ames Dwarf ◽  
Snell Dwarf ◽  
Dwarf Mice ◽  
Endonuclease Analysis ◽  
Control Litter

Restriction endonuclease analysis of genomic DNA was carried out for three types of dwarf mice (Little, Ames dwarf and Snell dwarf) that have genetic defects in GH expression. We found the GH genes to be present in homozygotes for each mutant allele as well as in their control litter-mates. These three types of dwarf mice may be useful in studying the molecular basis of inherited GH deficiency and as models for analogous genetic disorders of human GH expression.

scholarly journals Early Postnatal Administration of Growth Hormone Increases Tuberoinfundibular Dopaminergic Neuron Numbers in Ames Dwarf Mice

Endocrinology ◽  
2010 ◽  
Vol 151 (7) ◽  
pp. 3277-3285 ◽  
Author(s):  
Christina E. Khodr ◽  
Sara Clark ◽  
Alex F. Bokov ◽  
Arlan Richardson ◽  
Randy Strong ◽  
...  
Keyword(s):  
Third Ventricle ◽  
Dopamine Neurons ◽  
Zona Incerta ◽  
Brdu Incorporation ◽  
Neuron Development ◽  
Ames Dwarf Mice ◽  
Ames Dwarf ◽  
Catecholamine Histofluorescence ◽  
Pituitary Prolactin ◽  
Dwarf Mice

Hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons secrete dopamine, which inhibits pituitary prolactin (PRL) secretion. PRL has demonstrated neurotrophic effects on TIDA neuron development in PRL-, GH-, and TSH-deficient Ames (df/df) and Snell (dw/dw) dwarf mice. However, both PRL and PRL receptor knockout mice exhibit normal-sized TIDA neuron numbers, implying GH and/or TSH influence TIDA neuron development. The current study investigated the effect of porcine (p) GH on TIDA neuron development in Ames dwarf hypothalamus. Normal (DF/df) and dwarf mice were treated daily with pGH or saline beginning at 3 d of age for a period of 42 d. After treatment, brains were analyzed using catecholamine histofluorescence, tyrosine hydroxylase immunocytochemistry, and bromodeoxyuridine (BrdU) immunocytochemistry to detect BrdU incorporation. DF/df males and df/df treated with pGH experienced increased (P ≤ 0.01) weight gain compared with those treated with saline. DF/df had greater (P ≤ 0.01) TIDA neuron numbers than df/df, regardless of treatment. TIDA neuron number in pGH-treated df/df was greater (P ≤ 0.01) than in saline-treated df/df. Zona incerta and periventricular dopamine neurons were not affected by treatment or genotype. There was no effect of genotype or treatment on BrdU incorporation in the arcuate nucleus, median eminence, or periventricular region surrounding the third ventricle. Saline-treated df/df experienced decreased (P ≤ 0.05) dentate gyrus BrdU incorporation compared with saline-treated DF/df. In the lateral ventricle, pGH-treated males had greater BrdU immunoreactivity than pGH-treated females. The results show an effect of pGH on TIDA neuron development, although this effect is less potent than that of PRL, and likely GH-induced preservation of TIDA neurons rather than generation of new TIDA neurons via neurogenesis.

scholarly journals Tcf4 Is Involved in Subset Specification of Mesodiencephalic Dopaminergic Neurons

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 317
Author(s):  
Simone Mesman ◽  
Iris Wever ◽  
Marten P. Smidt
Keyword(s):  
Neuronal Differentiation ◽  
Dopaminergic Neurons ◽  
Neuronal Development ◽  
Neuronal Population ◽  
Minor Role ◽  
Initial Increase ◽  
E Box ◽  
A Minor ◽  
Bhlh Factor

During development, mesodiencephalic dopaminergic (mdDA) neurons form into different molecular subsets. Knowledge of which factors contribute to the specification of these subsets is currently insufficient. In this study, we examined the role of Tcf4, a member of the E-box protein family, in mdDA neuronal development and subset specification. We show that Tcf4 is expressed throughout development, but is no longer detected in adult midbrain. Deletion of Tcf4 results in an initial increase in TH-expressing neurons at E11.5, but this normalizes at later embryonic stages. However, the caudal subset marker Nxph3 and rostral subset marker Ahd2 are affected at E14.5, indicating that Tcf4 is involved in correct differentiation of mdDA neuronal subsets. At P0, expression of these markers partially recovers, whereas expression of Th transcript and TH protein appears to be affected in lateral parts of the mdDA neuronal population. The initial increase in TH-expressing cells and delay in subset specification could be due to the increase in expression of the bHLH factor Ascl1, known for its role in mdDA neuronal differentiation, upon loss of Tcf4. Taken together, our data identified a minor role for Tcf4 in mdDA neuronal development and subset specification.

scholarly journals Calcium-free vitrification reduces cryoprotectant-induced zona pellucida hardening and increases fertilization rates in mouse oocytes

Reproduction ◽  
2006 ◽  
Vol 131 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Mark G Larman ◽  
Courtney B Sheehan ◽  
David K Gardner
Keyword(s):  
Ethylene Glycol ◽  
Zona Pellucida ◽  
Cell Number ◽  
Blastocyst Stage ◽  
Initial Increase ◽  
Cell Stage ◽  
Free Treatment ◽  
Zona Hardening ◽  
Free Media ◽  
Oocyte Freezing

Despite the success of embryo cyropreservation, routine oocyte freezing has proved elusive with only around 200 children born since the first reported birth in 1986. The reason for the poor efficiency is unclear, but evidence of zona pellucida hardening following oocyte freezing indicates that current protocols affect oocyte physiology. Here we report that two cryoprotectants commonly used in vitrification procedures, dimethyl sulfoxide (DMSO) and ethylene glycol, cause a large transient increase in intracellular calcium concentration in mouse metaphase II (MII) oocytes comparable to the initial increase triggered at fertilization. Removal of extracellular calcium from the medium failed to affect the response exacted by DMSO challenge, but significantly reduced the ethylene glycol-induced calcium increase. These results suggest that the source of the DMSO-induced calcium increase is solely from the internal calcium pool, as opposed to ethylene glycol that causes an influx of calcium across the plasma membrane from the external medium. By carrying out vitrification in calcium-free media, it was found that zona hardening is significantly reduced and subsequent fertilization and development to the two-cell stage significantly increased. Furthermore, such calcium-free treatment appears not to affect the embryo adversely, as shown by development rates to the blastocyst stage and cell number/allocation. Since zona hardening is one of the early activation events normally triggered by the sperm-induced calcium increases observed at fertilization, it is possible that other processes are negatively affected by the calcium rise caused by cryoprotectants used during oocyte freezing, which might explain the current poor efficiency of this technique.

scholarly journals GH gene expression in the submaxillary gland in normal and Ames dwarf mice

2001 ◽  
Vol 169 (2) ◽  
pp. 389-396 ◽  
Author(s):  
A Perez-Romero ◽  
E Dialynas ◽  
F Salame ◽  
A Amores ◽  
L Vidarte ◽  
...  
Keyword(s):  
Southern Blot ◽  
Submaxillary Gland ◽  
Rt Pcr ◽  
Submaxillary Glands ◽  
Ames Dwarf Mice ◽  
Igf I ◽  
Ames Dwarf ◽  
Heart Blood ◽  
Two Parameters ◽  
Dwarf Mice

High local GH-releasing hormone (GHRH) levels are capable of inducing transdifferentiation in salivary cells to synthesize GH. However, the factors implicated in this process remain unknown. To study this subject, normal and Ames dwarf mice were implanted in the submaxillary gland with a slow release pellet releasing 21 microgram GHRH (1-29)-NH(2)/day for 2 months. Control animals received placebo pellets at the same site. After 60 days, heart blood was collected and submaxillary glands were removed. Circulating levels of GH and IGF-I were significantly decreased (P<0.05) in dwarf mice in comparison with controls, and GHRH treatment did not modify either of these two parameters. Controls carrying GHRH pellets showed a significantly higher GH content (P<0.05) in the submaxillary gland than the placebo-treated normal mice. There were no differences between the IGF-I concentrations of placebo- and GHRH-treated salivary tissue from normal mice. Analysis of GH mRNA by RT-PCR followed by Southern blot revealed that GH transcripts were present in the salivary gland samples carrying the placebo pellets in both normal and dwarf mice. The expression of GH was significantly (P<0.05) increased by the GHRH pellets in salivary tissue from normal mice, but not in submaxillary glands from dwarf mice. Pit-1 mRNA was not detected in the GHRH-treated glands of normal and dwarf mice by RT-PCR or by Southern blot. Using these highly sensitive methods, we have been able to detect the transcription of both GH and Pit-1 in pituitaries from Pit-1-deficient Ames dwarf mice. The present experiment demonstrates that salivary tissue synthesizes GH when it is exposed to the influence of GHRH. Both basal and GHRH-induced salivary GH expression appear to be independent of Pit-1.

scholarly journals The role of miR‐146a‐5p on insulin signaling and inflammation in adipose tissue of longliving Ames dwarf mice.

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Allancer Divino De Carvalho Nunes ◽  
Lin Yu ◽  
Collin Lahde ◽  
Sarah Noureddine ◽  
Tatiana Saccon ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Signaling ◽  
Ames Dwarf Mice ◽  
Ames Dwarf ◽  
Dwarf Mice
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