Metformin Restores Responses to Insulin but Not to Growth Hormone in Sprague–Dawley Rats

2002 ◽  
Vol 291 (3) ◽  
pp. 722-726 ◽  
Author(s):  
Stephen E. Borst ◽  
Harold G. Snellen ◽  
Henry Ross ◽  
Philip J. Scarpace ◽  
Yong-Woon Kim
1974 ◽  
Vol 75 (4) ◽  
pp. 669-682 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson

ABSTRACT The growth stimulating effect of growth hormone was determined with tetracycline as intravital marker of the longitudinal bone growth of proximal tibia in female Sprague-Dawley rats hypophysectomized at 60 days of age. After a post-operative control period of 15 days growth hormone (NIH-GH-B16) was given daily for 5 or 10 days followed by a 10 day period after its withdrawal. L-thyroxine was given in association with the growth hormone administration to potentiate the growth stimulation. A linear log dose-response relation was found for the two administration models with a high precision. The thyroxine-treatment increased the sensitivity of the bioassay. An administration period of 5 days was found sufficient for the bioassay of growth hormone in thyroxine-treated hypophysectomized rats. Compared with the earlier bioassay methods for growth hormone, the present bioassay is more favourable when all the factors, such as precision, sensitivity, specificity, and administration period are considered.


2014 ◽  
Vol 34 (4) ◽  
pp. 355-367 ◽  
Author(s):  
In Sik Hwang ◽  
Ji Eun Kim ◽  
Young Ju Lee ◽  
Moon Hwa Kwak ◽  
Jun Go ◽  
...  

Endocrinology ◽  
2021 ◽  
Vol 162 (4) ◽  
Author(s):  
Daniel D Lantvit ◽  
Christopher J Unterberger ◽  
Michelle Lazar ◽  
Paige D Arneson ◽  
Colin A Longhurst ◽  
...  

Abstract Previously, we reported that N-methyl-N-nitrosourea (MNU)-induced mammary tumors could be established in mutant spontaneous dwarf rats (SDRs), which lack endogenous growth hormone (GH) by supplementing with exogenous GH, and almost all such tumors regressed upon GH withdrawal. When the highly inbred SDR line was outcrossed to wild-type (WT) Sprague-Dawley rats, MNU-induced mammary tumors could still be established in resulting outbred SDRs by supplementing with exogenous GH. However, unlike tumors in inbred SDRs, 65% of mammary tumors established in outbred SDRs continued growth after GH withdrawal. We further tested whether these tumors were more sensitive to doxorubicin than their WT counterparts. To accomplish this, MNU-induced mammary tumors were established in WT rats and in SDRs supplemented with exogenous GH. Once mammary tumors reached 1 cm3 in size, exogenous GH was withdrawn from SDRs, and the subset that harbored tumors that continued or resumed growth in the absence of GH were selected for doxorubicin treatment. Doxorubicin was then administered in 6 injections over 2 weeks at 2.5 mg/kg or 1.25 mg/kg for both the WT and SDR groups. The SDR mammary tumors that had been growing in the absence of GH regressed at both doxorubicin doses while WT tumors continued to grow robustly. The regression of SDR mammary tumors treated with 1.25 mg/kg doxorubicin was accompanied by reduced proliferation and dramatically higher apoptosis relative to the WT mammary tumors treated with 1.25 mg/kg doxorubicin. These data suggest that downregulating GH signaling may decrease the doxorubicin dose necessary to effectively treat breast cancer.


1974 ◽  
Vol 75 (4) ◽  
pp. 653-668 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson

ABSTRACT The longitudinal bone growth of proximal tibia determined by tetracycline in hypophysectomized rats was used for the bioassay of growth hormone. Female Sprague-Dawley rats were hypophysectomized at 60 days of age and after a post-operative control period of 15 days growth hormone (NIH-GH-B16) was given daily for 5 or 10 days followed by a 10 day period after its withdrawal. A linear log dose-response relation was found for the two administration models with high precision. In the present investigation the longitudinal bone growth was more favourable as a growth parameter for the bioassay of growth hormone than the body weight and the width of the proximal tibial growth plate.


Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4375
Author(s):  
Hyesook Lee ◽  
Hyun Hwangbo ◽  
Seon Yeong Ji ◽  
Min Yeong Kim ◽  
So Young Kim ◽  
...  

Bone growth during childhood and puberty determines an adult’s final stature. Although several prior studies have reported that fermented oyster (FO) consisting of a high amount of gamma aminobutyric acid can be attributed to bone health, there is no research on the efficacy of FO on growth regulation and the proximal tibial growth plate. Therefore, in this study, we investigated the effect of FO oral administration on hepatic and serum growth regulator levels and the development of the proximal tibial growth plate in young Sprague-Dawley rats. Both oral administration of FO (FO 100, 100 mg/kg FO and FO 200, 200 mg/kg FO) and subcutaneous injection of recombinant human growth hormone (rhGH, 200 μg/kg of rhGH) for two weeks showed no toxicity. Circulating levels of growth hormone (GH) significantly increased in the FO 200 group. The expression and secretion of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) were enhanced by FO administration. FO administration promoted the expression of bone morphogenic proteins IGF-1 and IGFBP-3 in the proximal tibial growth plate. This positive effect of FO resulted in incremental growth of the entire plate length by expanding the proliferating and hypertrophic zones in the proximal tibial growth plate. Collectively, our results suggested that oral administration of FO is beneficial for bone health, which may ultimately result in increased height.


1997 ◽  
Vol 152 (3) ◽  
pp. 423-430 ◽  
Author(s):  
K Kondo ◽  
A Levy ◽  
S L Lightman

We have used in situ hybridization histochemistry to investigate the effects of maternal thyroidectomy and chronic maternal iodine deficiency on basal neuroendocrine function in rat pups. Specifically, we have measured hypothalamic thyrotrophin-releasing hormone (TRH) and pituitary thyroid-stimulating hormone (TSH) expression together with circulating levels of tri-iodothyronine (T3) in rat pups delivered from and suckled by thyroidectomized or iodine-deficient dams. Because of the close interaction between the thyroid, adrenal and growth hormone axes, we have also examined hypothalamic corticotrophin-releasing hormone (CRH) and growth hormone-releasing hormone (GRH) transcripts at the same time points: birth, 1 month and 2 months of age. Three weeks after surgical thyroidectomy, adult female Sprague–Dawley rats proved unable to carry pups to term and lactate successfully. Pups delivered from thyroidectomized dams given a small replacement dose of T3 during pregnancy were significantly lighter than controls (84 ± 3%) and had markedly depressed plasma T3 levels (36 ±6% of control). Hypothalamic CRH and GRH transcript levels were significantly decreased in pups at birth (to 8±2·5% and 24 ± 8% of control respectively) but had returned to normal by 1 month after delivery. Pituitary TSH transcript levels and hypothalamic levels of TRH transcripts, however, were similar to those of controls. Only one of seven dams fed a low-iodine diet for 6 months produced live pups, and these were too few in number to produce significant data. Dams fed a lowiodine diet from 4 months before mating, however, did produce live pups and although they were not significantly lighter than control pups at birth, by 1 month after birth, they were significantly lighter (72 ± 3% of controls). Circulating T3 levels were not significantly different from control at any time point examined. Hypothalamic TRH levels were significantly elevated at birth (451 ± 138% of control), but this difference was not maintained at 1 or 2 months after birth despite the lactating dams being maintained on the low-iodine diet. Pituitary TSH levels showed an upward trend at all time points that reached significance at 1 month after birth (204 ± 19%; P<0·05). Hypothalamic CRH and GRH transcript levels were not different from controls at any time point. In summary, chronic iodine deficiency or thyroidectomy with low-level T3 replacement in Sprague–Dawley rats markedly impaired fertility and the ability to carry pups to term, and produced an unexpectedly modest up-regulation of the hypothalamo–pituitary–thyroid axis and down-regulation of the hypothalamo–pituitary–adrenal axis. Journal of Endocrinology (1997) 152, 423–430


1974 ◽  
Vol 62 (2) ◽  
pp. 213-223 ◽  
Author(s):  
SAKAE KIKUYAMA ◽  
HIROSHI NAGASAWA ◽  
REIKO YANAI ◽  
KOREHITO YAMANOUCHI

SUMMARY Female Sprague—Dawley rats were fed 6-propyl-2-thiouracil (PTU) in their diet during late pregnancy and lactation. The growth and gonadal development of their pups were inhibited and in females the day of vaginal opening and onset of oestrous cycles were delayed; thyroid glands were hypertrophied. Treatment of the pups with thyroxine largely reversed these changes. The effect on body weight persisted even after treatment with PTU had stopped. At 20 days of age, the anterior pituitary glands of the pups of PTU-treated mothers contained significantly less growth hormone (GH) and prolactin than those of normal pups of both sexes. These changes persisted at 60 days of age. If the pups of PTU-treated mothers were given thyroxine from day 1 to day 20 of age, pituitary GH and prolactin content on day 20 had returned towards normal values. Thyroid deficiency was found to suppress the synthesis and release of prolactin and the synthesis of GH by the pituitary in vitro. These findings suggest that thyroxine influenced the maturation of the pituitary directly and/or through the hypothalamus and that thyroxine deficiency in early life brought about persistent alteration of the pituitary secretion of GH and prolactin.


1973 ◽  
Vol 57 (2) ◽  
pp. 253-264 ◽  
Author(s):  
R. C. HALLOWES ◽  
D. Y. WANG ◽  
D. J. LEWIS

SUMMARY Explants of mammary glands from mature virgin and pregnant Sprague—Dawley rats were maintained in organ culture for up to 96 h. The effects of insulin, corticosterone, ovine prolactin and bovine growth hormone on the synthesis of DNA, RNA and casein in the explants were studied. DNA synthesis in explants from virgin rats was maintained by insulin but was not increased by the addition of the other hormones tested. DNA synthesis in explants from pregnant rats was increased by insulin, and the addition of corticosterone and either prolactin or growth hormone to the culture medium increased this synthesis. The rate of RNA synthesis in explants from virgin rats was similar in medium 199 with or without additional hormones. RNA synthesis in explants from pregnant rats was increased by the addition of insulin or insulin plus corticosterone to the medium. In explants from both virgin and pregnant rats the maximal rate of hormone-stimulated DNA or RNA synthesis occurred during the first 24 h of culture. Casein synthesis, as measured by the uptake of 32P-labelled orthophosphate by explants from virgin and pregnant rats, was increased by insulin plus corticosterone plus either prolactin or growth hormone. The rate of casein synthesis was maximal between 48 and 72 h and was reduced by actinomycin D. In the pregnant rats no significant differences were demonstrated between the effects of the hormones on DNA, RNA or casein synthesis in explants from the 5th, 10th, 16th or 19th day of pregnancy.


1998 ◽  
Vol 275 (1) ◽  
pp. E6-E11 ◽  
Author(s):  
Thomas J. Lauterio ◽  
Ariel Barkan ◽  
Mark DeAngelo ◽  
Roberta DeMott-Friberg ◽  
Ray Ramirez

Sprague-Dawley rats, which become obese (obesity prone) when fed a moderately high-fat (MHF; 32.5% of kcal as fat) diet, have decreased growth hormone (GH) concentrations compared with obesity-resistant rats fed the same diet. To determine whether plasma GH concentrations are different in obesity-prone rats compared with obesity-resistant rats before diet-induced obesity occurs, total integrated GH concentrations were determined in male Sprague-Dawley rats before exposure to the MHF diet. After initial blood sampling, rats were fed an MHF diet for 15 wk, over which time the animals were separated into two discrete populations based on body weight gain. Analysis of GH in episodic blood samples showed that the obesity-prone group had a GH secretion deficit before the onset of obesity (115.2 ± 12.9 ng ⋅ ml−1 ⋅ 200 min−1) compared with obesity-resistant rats (237.2 ± 47.1 ng ⋅ ml−1 ⋅ 200 min−1). The GH concentration difference was due to a decrease in mean GH peak height in rats that later became obese (34.8 ng/ml) compared with rats that remained lean (74.2 ng/ml). The results suggest that GH secretion impairment exists before dietary challenge or onset of obesity and may contribute to the susceptibility to obesity observed in these animals.


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