Growth hormone (GH) secretion in the dwarf rat: release, clearance and responsiveness to GH-releasing factor and somatostatin

1990 ◽  
Vol 127 (1) ◽  
pp. 69-75 ◽  
Author(s):  
D. F. Carmignac ◽  
I. C. A. F. Robinson
Keyword(s):  
Low Dose ◽  
Gh Deficiency ◽  
Peak Plasma ◽  
Female Rats ◽  
Disappearance Rate ◽  
Gh Secretion ◽  
Fold Reduction ◽  
Plasma Gh ◽  
Age Range ◽  
Dose Dependent

ABSTRACT The new mutant GH-deficient dwarf (Dw) rat was used to study the effects of GH-releasing factor (GRF) or somatostatin (SRIF) on GH release. In anaesthetized adult Dw female rats, i.v. injections of GRF (0·031–2·0μg) elicited a dose-dependent release of GH. Although the peak plasma GH responses to maximal GRF doses were much lower in adult Dw rats compared with normal rats of this strain (AS), the responses largely reflected their relative pituitary GH contents (140±17 μg vs 2·9±0·4 μg, AS vs Dw (means ± s.e.m.), P < 0·001). Except at 20 days of age, normal AS rats were more sensitive to GRF than Dw rats despite their larger body weight. Peak GH responses to injection of 31·25 ng GRF increased nine-fold in normal rats between 20 and 40 days, whereas the GH responses to this GRF dose diminished in Dw rats over this age range, and their pituitary GH content was only 2–5% of that of age-matched AS rats. Treatment with human GH (200 μg/day for 7 days) stimulated growth in 40-day-old Dw rats and slightly increased the GH response to a low dose of GRF. Basal GH levels in adult Dw animals were sevenfold lower than in AS rats (2·4±0·3 vs 17·6±3·3 μg/l P < 0·001) and were further suppressed by i.v. infusion of SRIF (25 μg/h). As in normal rats, a rebound GH secretion occurred in Dw rats after stopping SRIF, which was blocked by injection of anti-GRF serum. The disappearance rate of 125I-labelled rat GH from plasma was identical in AS and Dw rats. We conclude that dwarf rats show GH deficiency as early as 20 days of age; they respond to GRF, but release only small amounts of GH due to their reduced pituitary GH content. Although basal GH release is reduced in Dw rats, the levels are higher than would be expected from the 50-fold reduction in pituitary stores, and may reflect a chronic reduction in SRIF and/or increase in GRF release induced by prolonged GH deficiency in the Dw rat. Journal of Endocrinology (1990) 127, 69–75

Post-somatostatin rebound secretion of growth hormone is dependent on growth hormone-releasing factor in unrestrained female rats

1989 ◽  
Vol 122 (2) ◽  
pp. 583-591 ◽  
Author(s):  
H. Sugihara ◽  
S. Minami ◽  
I. Wakabayashi
Keyword(s):  
Growth Hormone ◽  
Adult Female ◽  
Wistar Rats ◽  
Bolus Injection ◽  
Female Rats ◽  
Dependent Manner ◽  
Gh Secretion ◽  
Female Wistar Rats ◽  
Plasma Gh ◽  
Dose Dependent

ABSTRACT To examine the characteristics of GH secretion following the termination of the infusion of somatostatin, unrestrained adult female Wistar rats were subjected to repeated infusions of somatostatin separated by 30-min control periods. When somatostatin was infused for 150 min at a dose of 3, 30 or 300 μg/kg body wt per h, the magnitude of the rebound GH secretion increased in a dose-dependent manner. The infusion of somatostatin at a dose of 300 μg/kg body wt per h for 60, 150 or 240 min progressively augmented the size of the rebound GH secretion. When an antiserum to rat GH-releasing factor (GRF) was injected i.v. 10 min before the end of the infusion, the peak amplitude of the rebound GH secretion (300 μg/kg body wt, 150 min) was reduced to less than 20% of that of control rats. The rebound GH secretion (300 μg/kg body wt per h, 150 min) was augmented by a bolus injection of human GRF (1 μg/kg body wt). The combined effect of the end of infusion of somatostatin and a bolus injection of GRF on the amount of GH secreted was additive. The plasma GH response to GRF was completely inhibited when human GRF (3 μg/kg body wt per h) and somatostatin (300 μg/kg body wt per h) were infused simultaneously for 150 min. The magnitude of the rebound GH secretion following the termination of the co-administration was larger than that following the somatostatin infusion alone, but this rebound was not enhanced by a bolus injection of human GRF. Moreover, the amount of GH secreted was significantly less than that after the termination of somatostatin infusion plus a bolus injection of human GRF in the absence of preceding GRF administration. These results suggest that at least part of the influence of somatostatin on GH secretion is exerted at the level of the hypothalamus through modulating the release of GRF. In addition, it is inferred that the simultaneous infusion of GRF and somatostatin induces the attenuation of the GH response to GRF through a receptor effect. Journal of Endocrinology (1989) 122, 583–591

DISAPPEARANCE RATE OF BOVINE PROLACTIN FROM PLASMA OF FEMALE RATS STUDIED AT INTERVALS OF UP TO 160 MINUTES BY RADIOIMMUNOASSAY

1970 ◽  
Vol 64 (4) ◽  
pp. 718-725 ◽  
Author(s):  
A. A. van der Gugten ◽  
H. G. Kwa
Keyword(s):  
Intravenous Administration ◽  
Female Rats ◽  
Disappearance Rate ◽  
Blood Samples ◽  
Dose Dependent

ABSTRACT Plasma values resulting from the intravenous administration of 300, 100, 30 and 10 μ of bovine prolactin to rats on day 1 of pregnancy were followed by taking blood samples after 10, 20, 40, 80 and 160 minutes respectively. The rate of disappearance was found to be dose-dependent and to vary in time in the same rat. It is suggested that at least two processes of elimination take place: 1. a (possibly excretory) process, which can bring »unphysiologically high« prolactin levels down to approximately its treshold level of 1.7 μg/ml and 2. a process, which breaks down the hormone into »immunoreactive« polypeptides. This process can degrade 10 μg of bovine prolactin quantitatively within 10 minutes, but appears to become rapidly »saturated« by larger amounts of the hormone.

scholarly journals Perinatal exposure of female rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin induces central precocious puberty in the offspring

2008 ◽  
Vol 197 (2) ◽  
pp. 351-358 ◽  
Author(s):  
Masaki Kakeyama ◽  
Hideko Sone ◽  
Chiharu Tohyama
Keyword(s):  
Precocious Puberty ◽  
Low Dose ◽  
Female Offspring ◽  
Compensatory Hypertrophy ◽  
Female Rats ◽  
Perinatal Exposure ◽  
Dependent Manner ◽  
Early Maturation ◽  
Long Evans ◽  
Dose Dependent

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during the fetal and neonatal periods has been indicated to alter the development of the offspring later in life. In this study, we determined whether perinatal exposure to a low dose of TCDD affects the onset of puberty in the female offspring of Long-Evans hooded rats. On day 15 of gestation, pregnant female rats were administered TCDD by gavage at a single dose of 0 (vehicle), 200, or 800 ng/kg b.w. In the female offspring born to dams administered with TCDD at either 200 or 800 ng/kg b.w., the vaginal opening and first estrus occurred ∼4–7 days earlier than in the offspring born to vehicle-treated animals. The ovarian weight gain was also accelerated following exposure to TCDD in a dose-dependent manner. We next examined the ovarian compensatory hypertrophy (OCH) as an indicator of the maturation of the LH/GnRH-generating system in the pituitary and the hypothalamus. Exposure to TCDD accelerated the onset of OCH in the female offspring in a dose-dependent manner. In particular, in the offspring born to the dams exposed to TCDD at 800 ng/kg b.w., hypertrophy, which is characterized by hyperovulation and a marked increase in the weight of the remaining ovary after hemi-ovariectomy, was observed on postnatal days 27–30, which was 10 days earlier than in the offspring born to the vehicle-treated dams. These results indicate that perinatal exposure to a low dose of TCDD induces precocious puberty, including early maturation of the hypothalamic–pituitary axis, the gonads and genitals, in female Long-Evans hooded rats.

Growth hormone secretion in stalk-sectioned rats

1991 ◽  
Vol 124 (6) ◽  
pp. 700-706 ◽  
Author(s):  
Jun Kamegai ◽  
Ichiji Wakabayashi ◽  
Hitoshi Sugihara ◽  
Shiro Minami ◽  
Taiko Kitamura ◽  
...  
Keyword(s):  
Adrenal Glands ◽  
Gh Deficiency ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Male Rats ◽  
Gh Secretion ◽  
The Face ◽  
Prolactin Response ◽  
Plasma Gh ◽  
Trough Levels

Abstract. Idiopathic pituitary GH deficiency appears to result from neonatal disruption of hypophyseal portal vessels in the majority of patients. To examine the mechanism of GH deficiency associated with the disease, the effect of pituitary stalk section on GH secretion was studied in rats. Adult male rats were subjected to stalk section without inserting an impermeable membrane between the cut ends. They were studied 3 to 4 weeks after surgery. In stalk-sectioned rats, pituitary weight, body weight and hypothalamic SRIH content were significantly reduced as compared with sham-operated rats. Hypothalamic GHRH content, plasma T3, T4, corticosterone and testosterone levels, and weights of testes remove and adrenal glands were comparable in the two groups. Plasma GH profiles of sham-operated rats showed characteristic periodic pulses occurring at 2.5-3 h intervals with intervening trough period. In stalk-sectioned rats, plasma GH levels were low with small fluctuations, but GH levels were significantly higher than trough levels of sham-operated rats. The amount of GH secreted during a 6-h period as measured by planimetry was significantly reduced. To ascertain the regeneration of hypophyseal portal vessels, post SRIH rebound in GH secretion, which requires the presence of endogenous GHRH, was examined. Withdrawal of exogenous SRIH infusion triggered a large rebound GH secretion whose magnitude did not differ between groups. In stalk-sectioned rats, GH response to met-enkephalin analogue, FK 33-824, was not observed, whereas prolactin response to the secretagogue was observed in the majority of rats. It appears that in stalksectioned rats, hypophyseal portal circulation is re-established, but GHRH release from the hypothalamus is impaired in the face of sufficient supply of other hypophysiotropic hormones.

Plasma growth hormone (GH) and somatomedin C response to continuous growth hormone-releasing factor (GRF) infusion in patients with GH deficiency

1985 ◽  
Vol 110 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Naomi Hizuka ◽  
Kazue Takano ◽  
Kazuo Shizume ◽  
Izumi Tanaka ◽  
Noriko Honda ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Bolus Injection ◽  
Gh Deficiency ◽  
Saline Infusion ◽  
Pulse Area ◽  
Continuous Growth ◽  
Somatomedin C ◽  
Gh Secretion ◽  
The Mean ◽  
Plasma Gh

Abstract. Pituitary growth hormone (GH) responses during a 10-h iv infusion of saline or human GH-releasing factor (hGRF-44) at 500 ng/kg/h, followed by an iv bolus injection of hGRF-44 at 2 μg/kg body weight, were studied in 10 patients with GH deficiency. During saline infusion in 4 patients, small plasma GH increase were observed in 2 patients. However, during hGRF infusion in 6 patients, up to 4 or 13 pulses of GH secretion were observed. The mean integrated GH pulse area during hGRF infusion was 22.5 ± 5.2 (se) ng/ml × h, which was greater than that obtained during saline infusion. Plasma somatomedin C levels did not increase after hGRF infusion. After saline or hGRF infusion all patients responded to an iv bolus injection of the peptide. These results indicate that hGRF infusion augments GH secretion by increasing the number and amplitude of GH pulses and that the infusion does not cause pituitary somatotrophs to lose their capacity to respond to hGRF subsequently.

Growth hormone (GH) responses to the combined administration of GH-releasing hormone plus GH-releasing peptide 6 in adults with GH deficiency

1995 ◽  
Vol 132 (6) ◽  
pp. 712-715 ◽  
Author(s):  
A Leal-Cerro ◽  
E Garcia ◽  
R Astorga ◽  
FF Casanueva ◽  
C Dieguez
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Hormone Deficiency ◽  
Santiago De Compostela ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Factor I ◽  
Gh Replacement ◽  
Combined Administration ◽  
Plasma Gh

Leal-Cerro A, Garcia E, Astorga R, Casanueva FF, Dieguez C. Growth hormone (GH) responses to the combined administration of GH-releasing hormone plus GH-releasing peptide 6 in adults with GH deficiency. Eur J Endocrinol 1995;132:712–5. ISSN 0804–4643 In recent years the health problems of adults with growth hormone deficiency (GHD) and the benefits of GH replacement therapy have received considerable attention. However, the reliability of conventional GH tests in the assessment of pituitary GH reserve in this group of patients is still controversial. In this study, we assessed GH secretion after the combined administration of GH-releasing hormone (GHRH) (1 μg/kg iv) and GH-releasing peptide 6 (GHRP-6, 1 μg/kg iv) in adult patients diagnosed with GHD by conventional GH testing, and correlate this response with insulin-like growth factor I levels. Twenty-one subjects (13 male, 8 female) with long-standing diagnosis of GHD aged 21–54 years were studied. In 13 subjects GH responses to GHRH plus GHRP-6 were markedly reduced (peak GH response <10 mU/I), whereas in the remaining eight the response was greater (range 11–100 mU/l), In conclusion, our data show that combined administration of GHRH plus GHRP-6 elicited a significant increase in plasma GH levels in about 40% of patients diagnosed with GHD by conventional GH testing. C Dieguez, PO Box 563, 15700 Santiago de Compostela, Spain

scholarly journals Comparisons among old and new provocative tests of GH secretion in 178 normal adults

2000 ◽  
pp. 347-352 ◽  
Author(s):  
G Aimaretti ◽  
C Baffoni ◽  
L DiVito ◽  
S Bellone ◽  
S Grottoli ◽  
...  
Keyword(s):  
Low Dose ◽  
Adult Population ◽  
Ideal Body Weight ◽  
Normative Values ◽  
Gh Secretion ◽  
The Third ◽  
Ideal Body ◽  
The Mean ◽  
Age Range ◽  
Normal Adults

Classical provocative stimuli of GH secretion such as insulin-induced hypoglycaemia, arginine, clonidine, glucagon and levodopa have been widely used in clinical practice for approximately 30 years. On the other hand, in the last 10 years new potent stimuli of GH secretion have been proposed, but an extensive comparison with the classical ones has rarely been performed, at least in adults. In order to compare the GH-releasing activity of old and new provocative stimuli of GH secretion, and to define the normative values of the GH response, in 178 normal adults (95 males, 83 females; age range: 20-50 years, all within +/-15% of their ideal body weight), we studied the GH response to: insulin-induced hypoglycaemia (ITT, 0.1IU/kg i.v.), arginine (ARG, 0.5g/kg i.v.), clonidine (CLO, 300 microg/kg p.o.), glucagon (GLU, 1mg i.m.), pyridostigmine (PD, 120mg p.o.), galanin (GAL, 80pmol/kg per min), GH-releasing hormone (GHRH, 1 microg/kg i.v.), GHRH+ARG, GHRH+PD, hexarelin, a GH-releasing protein (HEX, 2 microg/kg i.v.) and GHRH+HEX (0.25 microg/kg i.v.). The mean (+/-s.e.m.) peak GH response to ITT (21.8+/-2.8, range: 3.0-84.0 microg/l) was similar to those to ARG (18.0+/-1.6, range: 2.9-39.5 microg/l) or GLU (20. 5+/-2.2, range: 10.6-36.9 microg/l) which, in turn, were higher (P<0. 001) than those to CLO (8.2+/-1.6, range: 0.3-21.5 microg/l), PD (9. 6+/-1.1, range: 2.2-33.0 microg/l) and GAL (9.3+/-1.1, range: 3.9-18. 3 microg/l). The GH response to GHRH (19.1+/-1.5, range: 2.7-55.0 microg/l) was similar to those after ITT, ARG or GLU but clearly lower than those after GHRH+ARG (65.9+/-5.5, range: 13.8-171.0 microg/l) and GHRH+PD (50.2+/-4.6, range: 17.7-134.5 microg/l) which, in turn, were similar. The GH response to HEX (55.3+/-5.5, range: 13.9-163.5 microg/l) was similar to those after GHRH+ARG and GHRH+PD but lower (P<0.001) than that after GHRH+HEX (86.0+/-4.3, range: 49. 0-125.0 microg/l) which was the most potent stimulus of GH secretion. In this adult population the third centile limits of peak GH response to various stimuli were the following: ITT: 5.3; ARG: 2.9; CLO: 1.5; GLU: 7.6; PD: 2.2; GAL: 4.0; GHRH: 5.0; GHRH+ARG: 17.8; GHRH+PD: 17.9; HEX: 21.6; GHRH+HEX: 57.1. These results confirm that, among classical provocative tests of GH secretion, ITT followed by ARG and GLU are the most potent ones and possess clear limits of normality. GHRH+ARG or PD and HEX are strong stimuli of GH secretion which, however, is maximally stimulated by a combination of GHRH and a low dose of HEX. It is recommended that each test is used with appropriate cut-off limits.

Subchronic Oral Toxicity Study of Mixed Tocopheryl Phosphates in Rats

2007 ◽  
Vol 26 (5) ◽  
pp. 475-490 ◽  
Author(s):  
R. Gianello ◽  
W. C. Hall ◽  
E. Kennepohl ◽  
R. Libinaki ◽  
E. Ogru
Keyword(s):  
Small Intestine ◽  
Lymph Node ◽  
Low Dose ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Female Rats ◽  
High Dose ◽  
Test Substance ◽  
Foreign Material ◽  
Dose Dependent

Rats were fed diets containing 0%, 1 %, 3%, or 5% mixed tocopheryl phosphates for 90 days. No abnormal clinical signs related to treatment appeared. Some statistically significant changes in hematology and clinical chemistry parameters appeared, but the majority were not dose dependent, occurred in only one sex or group, and/or remained within the historical control range for this strain of rat. A statistically significant apparent reduction in blood protein was observed in animals treated with the tocopheryl phosphates, but further investigation showed that the test substance interfered with the protein assay. Repeat analysis using a method unaffected by plasma test substance levels showed no difference in plasma proteins among all groups. Gross necropsy revealed no abnormalities; reduced relative heart and epididymal weights were observed, but were not dose dependent and were considered incidental. Histopathological changes occurred only in the mesenteric lymph node and small intestine. Foreign material in a crystal-like form appeared in macrophages in both organs, and increased in a dose-related fashion. In the lymph node, sinus histiocytosis increased with dose, but the severity was similar between the control and low-dose groups. Foreign-body granulomatous inflammation, associated with Maltese cross birefringence of the crystals was seen in the mid- and high-dose animals, but not the low-dose group. Similarly, the small intestine showed increasing amounts of foreign material and inflammation in the mid- and high-dose but not in the 1 % diet. The 1 % diet (equivalent to 587 and 643 mg mixed tocopheryl phosphates/kg body weight/day for male and female rats, respectively) was considered the no observed adverse effect level.

Single exposure to testosterone in adulthood rapidly induces regularity in the growth hormone release process

2000 ◽  
Vol 278 (5) ◽  
pp. E933-E940 ◽  
Author(s):  
Jean-Claude Painson ◽  
Johannes D. Veldhuis ◽  
Gloria S. Tannenbaum
Keyword(s):  
Growth Hormone ◽  
Adult Life ◽  
Approximate Entropy ◽  
Female Rats ◽  
Female Rat ◽  
Adult Rats ◽  
Release Process ◽  
Intact Group ◽  
Gh Secretion ◽  
Plasma Gh

The neonatal gonadal steroid milieu is known to be important in imprinting the striking sexual dimorphism of growth hormone (GH) secretion; however, the influence of the sex steroids on GH control in adult life and their mechanism/site of action are largely unknown. In the present study, we tested the hypothesis that testosterone (T) subserves the gender-specific regularity of the GH release process in adulthood. The approximate entropy statistic (ApEn) was used to quantify the degree of regularity of GH release patterns over time. Eighteen hours after a single subcutaneous injection of 1 mg T, both sham-operated and ovariectomized (OVX) female adult rats displayed plasma GH profiles that were strikingly similar to the regular male-like ultradian rhythm of GH secretion. The highest ApEn values, denoting greater disorderliness of GH secretion, were observed in the ovary-intact group, and T injection significantly ( P < 0.001) reduced this irregularity whether or not the ovaries were present. Serial intravenous injections of GH-releasing hormone (GHRH) caused a similar increase in plasma GH levels in sham-operated females independently of time of administration. In contrast, female rats administered T exhibited a male-like intermittent pattern of GH responsiveness to GHRH, the latter known to be due to the cyclic release of endogenous somatostatin. These results demonstrate that acute exposure to T during adult life can rapidly and profoundly “masculinize” GH pulse-generating circuits in the female rat. Our findings suggest that the enhanced orderliness characteristic of the GH release process in males, compared with females, is regulated by T. We postulate that this T-induced regularity is mediated at the level of the hypothalamus by inducing regularity in somatostatin secretion, which in turn governs overall GH periodicity.

Plasma growth hormone, somatostatin, insulin and glucagon inter-relationships during infusion of human pancreatic growth hormone-releasing factor in young and adult ducks (Anas platyrhynchos)

1987 ◽  
Vol 114 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Ch. Foltzer-Jourdainne ◽  
S. Harvey ◽  
H. Karmann ◽  
P. Mialhe
Keyword(s):  
Growth Hormone ◽  
Inhibitory Effect ◽  
Insulin Levels ◽  
Gh Secretion ◽  
Plasma Gh ◽  
Glucagon And Insulin ◽  
Rebound Increase ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Infusion Period

ABSTRACT Human pancreatic GH-releasing factor (hpGRF) increased the concentrations of plasma GH when infused i.v. into immature ducks. A dose-dependent increase in plasma GH was observed within 10 min of the start of infusion and was maintained during the 30-min infusion period. Simultaneous infusion of somatostatin S-14 prevented the increase in plasma GH induced by hpGRF, but when the infusion had finished there was a rebound increase in plasma GH. Infusion of the highest dose of hpGRF (800 ng/kg per min) in adult ducks had no significant effect on plasma GH. Plasma somatostatin concentrations were reduced during the infusion of hpGRF in young but not in adult ducks. This observation suggests that the stimulatory effect of hpGRF on GH secretion may be partly due to its inhibitory effect on somatostatin secretion. Infusion of hpGRF in ducklings also increased the concentrations of glucagon and decreased levels of insulin in the plasma. Peripheral plasma glucagon and insulin levels in adult ducks were unaffected by hpGRF infusion. These results indicate that in ducklings, hpGRF increases plasma GH and glucagon concentrations and lowers plasma somatostatin and insulin levels. In the adult, these hormonal responses to hpGRF are not maintained. The highly stimulatory effect of hpGRF on GH secretion in ducklings may explain why plasma GH concentrations are high in these birds. J. Endocr. (1987) 114, 25–32

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