Stimulatory Effect Of Growth Hormone Research Articles

Growth hormone stimulates lipolysis in mice but not in adipose tissue or adipocyte culture.

The inhibitory effect of growth hormone (GH) on adipose tissue growth and the stimulatory effect of GH on lipolysis are well known, but the mechanisms underlying these effects are not completely understood. In this study, we revisited the effects of GH on adipose tissue growth and lipolysis in the lit/lit mouse model. The lit/lit mice are GH deficient because of a mutation in the GH releasing hormone receptor gene. We found that the lit/lit mice had more subcutaneous fat and larger adipocytes than their heterozygous lit/+ littermates and that these differences were partially reversed by 4-week GH injection. We also found that GH injection to the lit/lit mice caused the mature adipose tissue and adipocytes to reduce in size. These results demonstrate that GH inhibits adipose tissue growth at least in part by stimulating lipolysis. To determine the mechanism by which GH stimulates lipolysis, we cultured adipose tissue explants and adipocytes derived from lit/lit mice with GH and/or isoproterenol, an agonist of the beta-adrenergic receptors. These experiments showed that whereas isoproterenol, expectedly, stimulated potent lipolysis, GH, surprisingly, had no effect on basal lipolysis or isoproterenol-induced lipolysis in adipose tissue explants or adipocytes. We also found that both isoproterenol-induced lipolysis and phosphorylation of hormone-sensitive lipase were not different between lit/lit and lit/+ mice. Taken together, these results support the conclusion that GH has lipolytic effect in mice but argue against the notion that GH stimulates lipolysis by directly acting on adipocytes or by enhancing β-adrenergic receptors-mediated lipolysis.

GCN2 and FGF21 are likely mediators of the protection from cancer, autoimmunity, obesity, and diabetes afforded by vegan diets

Third World quasi-vegan cultures have been characterized by low risks for “Western” cancers, autoimmune disorders, obesity, and diabetes. The relatively low essential amino acid contents of many vegan diets may play a role in this regard. It is proposed that such diets modestly activate the kinase GCN2 – a physiological detector of essential amino acid paucity – within the liver, resulting in up-regulated production of fibroblast growth factor 21 (FGF21). FGF21, by opposing the stimulatory effect of growth hormone on hepatic IGF-I production, may be responsible for the down-regulation of plasma IGF-I observed in vegans consuming diets of modest protein content. Decreased IGF-I bioactivity throughout life can be expected to have a favorable impact on cancer risk, as observed in rodents that are calorie restricted or genetically defective in IGF-I activity. Increased FGF21 in vegans might also contribute to their characteristic leanness and low LDL cholesterol by promoting hepatic lipid oxidation while inhibiting lipogenesis. Direct trophic effects of FGF21 on pancreatic beta-cells may help to explain the low risk for diabetes observed in vegans, and the utility of vegan diets in diabetes management. And up-regulation of GCN2 in immune cells, by boosting T regulatory activity, might play some role in the reduced risk for autoimmunity reported in some quasi-vegan cultures. The fact that bone density tends to be no greater in vegans than omnivores, despite consumption of a more “alkaline” diet, might be partially attributable to the fact that FGF21 opposes osteoblastogenesis and decreases IGF-I. If these speculations have merit, it should be possible to demonstrate that adoption of a vegan diet of modest protein content increases plasma FGF21 levels.

Orthodontic and surgical treatment of a patient with hemifacial microsomia

This article describes the surgical and orthodontic treatment of a 12-year-old boy with a significant deformity and functional involvement caused by hemifacial microsomia. The left mandibular ramus and condyle were hypoplastic and abnormal in form and location. The lower third of the face was increased, with mandibular retrusion and significant facial asymmetry. He had difficulties in speaking and chewing and problems related to his facial appearance, which caused severe psychosocial disturbances. The patient received orthodontic treatment and temporomandibular joint reconstruction with a costochondral graft on the left side while he was still growing. Three-year follow-up records are presented.

Growth Hormone Induces Hepatic Production of Fibroblast Growth Factor 21 through a Mechanism Dependent on Lipolysis in Adipocytes

Fibroblast growth factor (FGF) 21 and growth hormone (GH) are metabolic hormones that play important roles in regulating glucose and lipid metabolism. Both hormones are induced in response to fasting and exert their actions on adipocytes to regulate lipolysis. However, the molecular interaction between these two hormones remains unclear. Here we demonstrate the existence of a feedback loop between GH and FGF21 on the regulation of lipolysis in adipocytes. A single bolus injection of GH into C57 mice acutely increases both mRNA and protein expression of FGF21 in the liver, thereby leading to a marked elevation of serum FGF21 concentrations. Such a stimulatory effect of GH on hepatic FGF21 production is abrogated by pretreatment of mice with the lipolysis inhibitor niacin. Direct incubation of either liver explants or human HepG2 hepatocytes with GH has no effect on FGF21 expression. On the other hand, FGF21 production in HepG2 cells is significantly induced by incubation with the conditioned medium harvested from GH-treated adipose tissue explants, which contains high concentrations of free fatty acids (FFA). Further analysis shows that FFA released by GH-induced lipolysis stimulates hepatic FGF21 expression by activation of the transcription factor PPARα. In FGF21-null mice, both the magnitude and duration of GH-induced lipolysis are significantly higher than those in their wild type littermates. Taken together, these findings suggest that GH-induced hepatic FGF21 production is mediated by FFA released from adipose tissues, and elevated FGF21 in turn acts as a negative feedback signal to terminate GH-stimulated lipolysis in adipocytes.

Effects of Growth Hormone and Thyroxine Replacement Therapy on Insulin Signaling in Ames Dwarf Mice

Ames dwarf (Prop1(df), df/df) mice lack growth hormone (GH), prolactin, and thyrotropin and live remarkably longer than their normal siblings. Significance of reduced activity of the somatotropic and thyroid axes during development and adulthood on longevity are unknown. Because enhanced insulin sensitivity and reduced insulin levels are among likely mechanisms responsible for increased longevity in these mutants, we compared the effects of GH and thyroxine (T4) replacement on various parameters related to insulin signaling in young and old male df/df mice. The results suggest that altered plasma adiponectin and insulin-like growth factor-1 (IGF-1) and hepatic IGF-1, insulin receptor (IR), IR substrate-1, peroxisome proliferator-activated receptor (PPAR) gamma, and PPARgamma coactivator-1 alpha may contribute to increased insulin sensitivity in Ames dwarfs. The stimulatory effect of GH and T4 treatment on plasma insulin and inhibitory effect on expression of hepatic glucose transporter-2 were greater in old than in young dwarfs. These results indicate that GH and T4 treatment has differential impact on insulin signaling during development and adulthood.

Adrenal morphology and function in acromegalic patients in relation to disease activity

Visceromegaly is a common consequence of acromegaly. However, few studies investigated the chronic effects of growth hormone on adrenal glands. Our aim was to evaluate adrenal morphology and function in a cohort of acromegalic patients in relation to disease activity. Twenty-six acromegalics (10 males and 16 females) and 21 healthy subjects were investigated. Gland morphology was evaluated by computerized axial tomography, measuring central, lateral, and medial adrenal segments. Uncontrolled acromegalics showed increased volume of all adrenal segments, higher urinary free cortisol (UFC), and lower morning adrenocorticotropic hormone in comparison with healthy subjects. However, normal cortisol levels after low-dose dexamethasone suppression test indicated a preserved regulation of the hypothalamic-pituitary-adrenal axis. In addition, uncontrolled patients showed greater medial segment of right gland, higher UFC, and aldosterone levels with respect to controlled patients. All acromegalics did not show any difference in adrenal size when grouped according to UFC/24 h levels. In addition, no difference was found in any of the parameters between normotensive and hypertensive patients. In conclusion, our findings confirm that acromegaly affects adrenal size as well as other organs. In addition, we report a stimulatory effect of growth hormone on adrenal function, although the regulation of the hypothalamic-pituitary-adrenal axis is preserved.

Growth hormone-related effects on apoptosis, mitosis, and expression of connexin 43 in bovine in vitro maturation cumulus-oocyte complexes.

Pituitary LH and FSH are known to be the major regulators of ovarian function. In the last few years, however, there has been evidence that growth hormone (GH) is also involved in ovarian regulation. Therefore, the aim of our study was to elucidate the mechanisms of GH action during in vitro maturation (IVM) of bovine cumulus-oocyte complexes (COCs). As shown by detection of the nuclear cell proliferation-associated antigen Ki-67, COCs matured in vitro in the presence of GH revealed a significantly (P < 0.05) higher proportion of proliferating cumulus cells (12.6%) compared with the COCs matured in the control medium TCM 199 (9.9%). In contrast, the percentage of proliferating cells was not increased by supplementation of the medium with a combination of GH and insulin-like-growth factor I (IGF-I). Apoptosis as determined by TUNEL (terminal doxynucleotidyl transferase mediated dUTP nick-end labeling) was significantly (P < 0.05) reduced in the cumulus cells by GH treatment. COCs matured with a combination of GH and IGF-I revealed the lowest percentage of apoptotic cells (11%). The localization and quantification of the gap junction protein connexin 43 (Cx 43) demonstrated that GH induced a significant decrease in the synthesis of the Cx 43 protein in the cumulus cells. Our results imply that GH increases cumulus expansion by promotion of cell proliferation and inhibition of apoptosis. Whereas the increase in cell proliferation is a direct effect of GH, the antiapoptotic effects of GH during in vitro maturation are modulated by IGF-I. Stimulatory effects of GH on oocyte maturation are correlated with changes in the synthesis of gap junction proteins.

Presumptive Mediators of Growth Hormone Action on Insulin-Like Growth Factor I Release by Porcine Ovarian Granulosa Cells

The role of cAMP/protein kinase A (PKA)- and tyrosine kinase (TK)-dependent intracellular mechanisms in mediating the action of porcine growth hormone (GH) on insulin-like growth factor I (IGF-I) secretion by porcine ovarian granulosa cells was studied. It was observed that GH-induced stimulation of IGF-I secretion was accompanied by an increase in cAMP production. The stimulation of PKA by the addition of either a cAMP agonist or a phosphodiesterase inhibitor to the medium increased IGF-I release by the cells, indicating a direct stimulation of IGF-I release by cyclic nucleotides. Moreover, the stimulatory effect of GH on IGF-I was completely suppressed by the addition of the PKA blocker Rp-cAMPS. Neither TK blocker altered the basal IGF-I level, but both strongly suppressed the GH-induced increase in IGF-I accumulation. Taken together, these findings suggest that cAMP/PKA- and/or TK-dependent pathways may be involved in the mediation of GH action on IGF-I release by porcine granulosa cells.

Possible Involvement of Insulin-like Growth Factor-I in Mediating the Stimulatory Effect of Recombinant Bovine Growth Hormone on Maturation of Bovine Oocytes In Vitro.

The present study was undertaken to determine whether insulin-like growth factor-I (IGF-I) is involved in mediating the stimulatory effects of growth hormone (GH) on nuclear maturation of bovine oocytes in vitro and subsequent embryonic development after in vitro fertilization. When cumulus-oocyte complexes (COCs) or cumulus-free oocytes were cultured in modified Medium 199 supplemented with 0-100 ng/ml recombinant human IGF-I (rhIGF-I), the proportion of COCs with slight cumulus expansion was increased with increasing concentration of rhIGF-I after 12 and 24 h of culture. Nuclear maturation of oocytes to the metaphase II (M-II) stage was promoted by rhIGF-I only in COCs, with higher proportions of M-II oocytes at 10-100 ng/ml (74 ± 3-76 ± 3%) than at 0-1 ng/ml (53 ± 4-61 ± 1%) after 24 h of culture. When COCs were cultured in the presence of 100 ng/ml rhIGF-I or 10 ng/ml recombinant bovine GH (rbGH) and/or anti-IGF-I antibody (Ab) for 24 h, the proportion of oocytes reaching the M-II stage was higher with rhIGF-I (73 ± 2%) or rbGH (74 ± 1%) than in the absence of these additives (54 ± 3%), in Ab alone (54 ± 3%), or with IGF-I or GH in combination with Ab (54 ± 3-58 ± 1%). The inhibition of the stimulatory effects of rbGH on nuclear maturation by Ab was dose-dependent. After in vitro maturation and fertilization, no differences were observed in the penetration rate (75 ± 3-77 ± 6%), pronuclear formation (56 ± 3-64 ± 10%) and polyspermy (28 ± 4-36 ± 5%) at 8 h post-insemination among cumulus enclosed oocytes cultured in the presence of different additives. When the oocytes were cultured in a chemically defined medium starting from 8 h after insemination, 20 ± 1-26 ± 2% of oocytes developed to the ≥ morula stage 144 h post-insemination without difference among different additives during maturation. However, at 192 h post-insemination, higher proportions of oocytes developed to the blastocyst stage when COCs were matured in the presence of rhIGF-I (16 ± 1%) or rbGH (15 ± 2%) than in the absence of the additives (4 ± 2%) or when IGF-I or GH was combined with Ab (4 ± 2-5 ± 3%). These results suggest that the stimulatory effects of GH on bovine oocyte maturation may not be direct, but mediated via IGF-I probably produced by the cumulus cells.

Stimulatory effect of growth hormone on in vitro maturation of bovine oocytes is exerted through the cyclic adenosine 3',5'-monophosphate signaling pathway.

The aim of this study was to investigate whether the stimulatory effect of growth hormone (GH) on the in vitro maturation and cumulus expansion of bovine oocytes is exerted through the cAMP or the tyrosine kinase pathway. Therefore bovine cumulus-oocyte complexes (COCs) were cultured in Medium 199 without fetal calf serum and gonadotropins, but supplemented with 100 ng/ml bovine GH (bGH; NIH-GH-B18) with or without 10 microM methyl 2,5-dihydroxycinnamate (erbstatin analogue), a specific tyrosine kinase inhibitor; 100 microM 2',3'-dideoxyadenosine (DDA), a specific adenylate cyclase inhibitor; or 10 microM H-89, a specific inhibitor of cAMP-dependent protein kinase A. Epidermal growth factor (EGF; 20 ng/ml) was added as a positive control for tyrosine kinase activation, and FSH (0.05 IU/ml) was added as a positive control for cAMP mediation during in vitro maturation in the absence or presence of the inhibitors. Culture was performed at 39 degrees C in a humidified atmosphere with 5% CO2 in air. To assess the effect on nuclear maturation, the proportion of oocytes in metaphase II stage after 16 h of culture was determined using 4,6-diamino-2-phenylindole staining. To determine the effect on cumulus expansion, the diameter of COCs at the onset and after 24 h of culture was measured. The stimulatory effects of GH on oocyte maturation and cumulus expansion were blocked by DDA and H-89 (p < 0.01). Similarly, FSH-induced cumulus expansion was abolished by DDA and H-89 (p < 0.05), while DDA did not block either EGF-induced oocyte maturation or cumulus expansion. Erbstatin analogue significantly blocked the stimulation of oocyte maturation and cumulus expansion by EGF (p < 0.02) but did not inhibit GH action on the COCs. It is concluded that the stimulatory effect of GH on oocyte maturation and cumulus expansion is mediated by the cAMP signal transduction pathway and not by JAK2 phosphorylation.

Stimulatory effect of growth hormone on in vitro maturation of bovine oocytes is exerted through cumulus cells and not mediated by IGF‐I

Stimulatory effect of growth hormone on in vitro maturation of bovine oocytes is exerted through cumulus cells and not mediated by IGF‐I

Stimulatory effect of growth hormone on in vitro maturation of bovine oocytes is exerted through cumulus cells and not mediated by IGF-I.

A previous study reported that the addition of bovine growth hormone (bGH) during in vitro maturation of bovine oocytes accelerates nuclear maturation and stimulates subsequent embryonic development. The aim of this study was to investigate whether bovine cumulus oocyte complexes (COCs) contain growth hormone receptor (GHR), and whether the stimulatory effect of GH on oocyte maturation is cumulus-dependent and mediated by insulin-like-growth factor (IGF-I). The expression of growth hormone receptor mRNA in mural granulosa cells, in cumulus cells, and in the oocyte was studied using reverse transcriptase polymerase chain reaction (RT-PCR). To investigate the importance of cumulus cells for GH-promoted maturation, COCs and denuded oocytes were cultured for 16 hr in M199 with or without bGH s(NIH-GH-B18). To investigate whether GH action is mediated by IGF-I, COCs were cultured in 1) 100 ng/ml bGH, 2) 100 ng/ml bGH plus anti-IGF-I, 1:100 dilution, 3) 100 ng/ml h-IGF-I, 4) 100 ng/ml h-IGF-I plus anti-IGF-I, 1:100 dilution, and 5) anti-IGF-I, 1:100 dilution. Culture was performed at 39 degrees C in a humidified atmosphere with 5% CO2 in air, and the nuclear stage of oocytes was assessed using 4,6-diamino-2-phenyl-indole (DAPI) staining. PCR on cDNA of mural granulosa cells, cumulus cells, and oocytes revealed that mRNA for GHR was present in all cell types. Addition of GH (100 ng/ml) to the culture medium of denuded oocytes did not affect the number of metaphase II oocytes after 16 hr, while a significant (P < 0.001) increase was observed, when COCs were cultured in the presence of GH. Addition of the antibody against IGF-I to the culture medium completely suppressed the stimulatory effect of IGF-I on oocyte maturation and cumulus expansion, while stimulation by GH was not affected by the antibody. It is concluded that bovine cumulus cells, mural granulosa, and oocytes express mRNA for the GH receptor. The stimulatory effect of GH on bovine oocyte maturation is dependent on the cumulus cells and is not mediated by IGF-I.

Growth hormone treatment increases cytochrome P450-mediated antipyrine clearance in man.

We used the antipyrine clearance test (APC) to examine the effect of growth hormone (GH) therapy on hepatic cytochrome P450 (CYP) enzyme activity. Eleven GH deficient adults were randomized to receive GH or placebo for 6 months, all subjects subsequently received GH. Before treatment, APC was below the normal range in six subjects. We found an increase in APC in the subjects randomized to receive GH compared to those on placebo (median change +0.14 ml/min/kg [range + 0.04 to + 0.20]vs -0.04 ml/min/kg [range -0.07 to + 0.04], p = 0.011). The stimulatory effect of GH on drug metabolism was confirmed by the data for 3 months GH treatment in all 11 subjects, with APC increasing from 0.33 ml/min/kg (range 0.22 to 0.69) to 0.50 ml/min/kg (range 0.27 to 0.83), p = 0.018). These data indicate that GH modulates hepatic CYP activity. This has important clinical implications, as the hepatic metabolism of drugs and hormones may be altered in patients undergoing GH therapy.

Stimulatory effect of growth hormone on bone resorption and osteoclast differentiation

Stimulatory effect of growth hormone on bone resorption and osteoclast differentiation

Stimulatory effect of growth hormone on bone resorption and osteoclast differentiation.

Although the actions of GH on osteoblasts have been extensively investigated, its effects on osteoclasts remain unknown. In the present study, the effects of GH on bone resorption and osteoclast differentiation were examined in vitro. Bovine GH (bGH; 1-100 ng/ml) significantly stimulated bone resorption by preexistent osteoclasts in stromal cell-containing mouse bone cell cultures, whereas it did not affect the bone-resorbing activity of isolated rabbit osteoclasts. When bGH was added to unfractionated bone cells after degeneration of preexistent osteoclasts, it concentration dependently stimulated osteoclast-like cell formation. GH also enhanced 1,25-dihydroxyvitamin D3-induced osteoclast-like cell formation. Moreover, osteoclast-like cells newly formed from unfractionated bone cells in the presence of bGH possessed the ability to form pits on dentine slices. The conditioned medium from osteoblastic MC3T3-E1 cells or MC3T3-G2/PA-6 stromal cells pretreated with bGH stimulated osteoclast-like cell formation from mouse hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor. On the other hand, the PCR products corresponding in size to the mouse GH receptor were detected in mouse hemopoietic blast cells as well as liver. GH concentration dependently stimulated osteoclast-like cell formation from these hemopoietic blast cells in the absence of stromal cells, and these osteoclast-like cells formed pits on dentine slices in the presence of MC3T3-G2/PA-6 stromal cells. The present study indicated for the first time that GH stimulates osteoclastic bone resorption through both its direct and indirect actions on osteoclast differentiation and through its indirect activation of mature osteoclasts, possibly via stromal cells, including osteoblasts.

Growth factors and renal regulation of phosphate transport.

During the development of vertebrates, the extracellular concentration of inorganic phosphate (Pi) is maintained at a higher level than during adult life. This elevation is probably essential for both cellular growth and mineralization of the skeleton. A high tubular Pi transport capacity (maxTRPi/GFR) and a high plasma level of 1,25-dihydroxyvitamin D3 are considered to play a major role in the high Pi retention observed during growth. Experimental studies have shown that the high maxTRPi/GFR observed in growing young compared with adult individuals is not associated with differences in other renal functions, suggesting the existence of a selective homeostatic process. Growth hormone (GH) had no direct effect on renal Pi reabsorption, indicating that GH stimulation of renal Pi transport in various physiological and pathophysiological conditions is induced by insulin-like growth factor-1 (IGF-1), the mediator of the anabolic effects of GH. In hypophysectomized rats, administration of IGF-1 mimicked the stimulatory effects of GH on maxTRPi per milliliter glomerular filtrate and on plasma 1,25-dihydroxyvitamin D3. As for GH, the change in maxTRPi per milliliter glomerular filtrate induced by IGF-1 was mediated by a parathyroid hormone-independent mechanism and was selectively expressed at the level of the luminal membrane of proximal tubules. These observations are evidence that IGF-1 mediates the effect of GH on the renal handling of Pi and production of 1,25-dihydroxyvitamin D3 and might play a significant role in the control of Pi metabolism during growth. Recent observations suggest that other growth factors might be involved in the regulation of tubular Pi transport.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of growth hormone on fracture healing in rats: A histological description

Previous biomechanical studies have indicated that growth hormone has a stimulatory effect on fracture healing. This study was designed to give a histological description of the long-term effects of growth hormone on fracture healing in rats. Sixty-four female rats were divided into two groups and were given either biosynthetic human growth hormone (2.7 mg/kg body weight/day) or saline s.c. in two daily injections. This treatment was given for 20 days after a closed tibial fracture with medullary nailing had been performed. Five or six rats were killed from each group after 10, 20, 30, 40, 50, and 80 days of healing. The fracture site was embedded undecalcified in methylmethacrylate, cut into 8 μm thick, midfrontal sections, and investigated in a normal light microscope after staining with Masson Trichrome and in polarized light after staining with Sirius red. The results revealed that growth hormone had an initially stimulatory effect on external callus formation. However, the callus formed was loosely structured and was not removed by the normal modeling and remodeling process. The callus therefore persisted even after 80 days of healing. In contrast, after only 40 days the saline treated rats showed healing, with a resumption of the normal size and shape of the fractured tibial bone, leaving only a small amount of dense callus tissue. The study also revealed that the hemopoietic system was stimulated by growth hormone, with massive invasion of marrow cells into the external fracture callus. Bone marrow cells dominated the intratrabecular space in growth-hormone treated animals, even after 80 days of healing. On the basis of this study, it is concluded that although there is an initially stimulatory effect of growth hormone on callus formation, the callus formed during growth hormone treatment is abnormal with an extremely loose structure, and modeling and remodeling of this callus are delayed. It seems that the bone marrow ceils grow at the expense of the mineralized callus tissue, or that the normal architecture of the callus tissue is disrupted.

Contributory roles of circulatory glucagon and growth hormone to increased renal haemodynamics in type 1 (insulin-dependent) diabetes mellitus.

The stimulatory effects of growth hormone (GH) and glucagon on renal function are well known, but it is uncertain whether these hormones are involved in the increase in renal function, characteristic of type 1 (insulin-dependent) diabetes mellitus. Therefore, the circulatory levels of GH and glucagon were measured in 10 type 1 diabetic patients with an elevated glomerular filtration rate (GFR > 130 ml min-1 1.73 m-2) and in 20 age and sex matched normofiltering patients (GFR ranging from 90-130 ml min-1 1.73 m-2). In the patients, fasting glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined using 125I-iothalamate and 131I-hippuran, respectively, during near-normoglycaemia. On a separate day, the levels of glucagon and GH were determined in the fasting basal state and after exercise. Multiple regression analysis disclosed that GFR was positively correlated with HbA1 (r2 = 0.18, p < 0.01), glucagon (r2 = 0.14, p < 0.03) as well as exercise-stimulated GH (r2 = 0.10, p < 0.05). ERPF was independently associated with HbA1 (r2 = 0.24, p < 0.005) and glucagon (r2 = 0.18, p < 0.01), whereas renal vascular resistance (RVR) was negatively correlated with stimulated GH (r2 = 0.18, p < 0.02). Kidney volume was positively correlated with HbA1 (r2 = 0.26, p < 0.001) and inversely with RVR (r2 = 0.16, p < 0.01), but not with glucagon or stimulated GH. The present study suggests that circulatory GH and glucagon play a contributory role in the renal haemodynamic changes in type 1 diabetes mellitus.

Endocrine mechanisms for the formation of sex-related differences in hepatic estrogen receptor content and their significance for the realization of an estrogen effect on angiotensinogen blood level in rats.

The use of a modified, adequate method of quantification of estrogen receptors has permitted us to prove the existence of sex-specific peculiarities in rat liver estrogen reception and their significance for the realization of sex-dependent changes in angiotensinogen plasma level after estrogenization. Endocrine mechanisms for the formation of sex-related differences in hepatic estrogen receptor content in rats were investigated in detail. The investigation shows that androgens have negative regulatory influence on the hepatic estrogen receptor level in rats. Estrogens and adrenal and thyroid hormones do not take part in the regulation of hepatic estrogen receptor content in rats. It has been proven that the decisive role in keeping up a certain estrogen receptor concentration in hepatocytes belongs to pituitary growth hormone. It was shown for the first time that androgens are able to inhibit the stimulatory effect of growth hormone on hepatic estrogen receptors.

Stimulatory effects of growth hormone on rat bladder carcinogenesis

The authors investigated the influences of recombinant human growth hormone (rh-GH) on rat urinary bladder carcinogenesis induced with N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Rats belonging to the control group (Group I, n = 19) were given 0.05% BBN in drinking water for 9 weeks, and the bladder was excised on the 22nd week after the initiation of BBN administration and inspected. All animals developed visible tumors in the bladder. The mean number of tumors per bladder was 11.26 +/- 5.21, and the mean total volume of tumors per bladder was 126.1 +/- 212.7 microliters. In all but one of the experimental groups (Group V) and in the control group, all animals developed visible tumors in the bladder. When 0.5 units of rh-GH was injected subcutaneously once a week from the week 1 through the week 6 (Group II; n = 20), the mean number of tumors and mean total volume of the tumors were 12.15 +/- 6.59 and 206.6 +/- 318.0 microliters, respectively. When the administration period of rh-GH was changed to between week 7 through the week 12 (Group III; n = 19), the mean number of tumors and mean total volume of the tumors were 16.95 +/- 7.07 and 204.5 +/- 317.7 microliters, respectively. When rh-GH was administered from the week 13 through the week 18 (Group IV; n = 19), the respective values were 16.79 +/- 10.75 and 213.4 +/- 274.6 microliters. In Group V (n = 19), which received only rh-GH from week 1 through the week 6, no tumors were detected. There were statistically significant differences in the mean tumor numbers between Groups I and III, Groups I and IV, and Groups II and III. The mean volume of individual tumor was the greatest in Group II, although the differences were not statistically significant in comparison with the other groups. Histologically, all tumors were transitional cell carcinoma in every group. There were no statistically significant differences in distributions of tumor stage and tumor grade between any groups. These findings suggest that rh-GH enhances the promotion of carcinogenesis of chemically induced rat urinary bladder cancer. It will be necessary to elucidate whether this effect of rh-GH is expressed by the somatostatin hypothesis of GH action, its direct action, or some other mechanisms.