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Biomedical subjects

O G Isaksson

Publications and source records attributed to O G Isaksson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Treatment of growth hormone-deficient adults with recombinant human growth hormone increases the concentration of growth hormone in the cerebrospinal fluid and affects neurotransmitters.

In a double-blind, placebo-controlled trial, the effects of recombinant human growth hormone were studied on cerebrospinal fluid concentrations of growth hormone, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), monoamine metabolites, neuropeptides and endogenous opioid peptides. Twenty patients, 10 patients in each of 2 groups, with adult-onset, growth hormone deficiency were treated for 1 month with recombinant human growth hormone (0.25 U/kg/week) or placebo. All the patients received the appropriate thyroid, adrenal and gonadal hormone replacement. In cerebrospinal fluid, the mean concentration of growth hormone increased from 13.3 +/- 4.4 to 149.3 +/- 22.2 muU/l (p = 0.002), during recombinant human growth hormone treatment. The cerebrospinal fluid IGF-I concentration increased from 0.67 +/- 0.04 to 0.99 +/- 0.10 micrograms/l (p = 0.005) and the IGFBP-3 concentration rose from 13.4 +/- 1.25 to 17.5 +/- 1.83 micrograms/l (p = 0.002). The dopamine metabolite homovanillic acid decreased from 282.1 +/- 36.0 to 234.3 +/- 26.5 nmol/l (p = 0.02) and the vasoactive intestinal peptide decreased from 4.1 +/- 0.6 to 3.7 +/- 0.4 pmol/l (p = 0.03). Cerebrospinal fluid immunoreactive beta-endorphin increased from 24.4 +/- 1.8 to 29.9 +/- 2.1 pmol/l (p = 0.002). There were no significant changes compared to baseline in the cerebrospinal fluid concentrations of enkephalins, dynorphin A, the norepinephrine metabolite 3-methoxy-4-hydroxyphenyl-ethyleneglycol, the serotonin metabolite 5-hydroxyindoleacetic acid, gamma-aminobutyric acid, somatostatin or corticotropin-releasing factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Hormonal regulation of longitudinal bone growth.

The regulation of postnatal somatic growth is complex. Genetic, nutritional factors and hormones exert regulatory functions. Hormones that have an established role in the regulation include growth hormone (GH), thyroid hormone and sex steroids. GH promotes mainly the growth of the long bones in terms of final height, while the action of the sex steroids and thyroid hormone is less well known. Longitudinal bone growth is the result of chondrocyte proliferation and subsequent endochondral ossification in the epiphyseal growth-plates. The growth-plate is a cartilaginous template that is located between the epiphysis and the metaphysis of the long bones. GH and insulin-like growth factor-I (IGF-I) have different target cells in the epiphyseal growth-plate. GH stimulates the slowly dividing prechondrocytes in the germinative cell layer while IGF-I promotes the clonal expansion in the proliferative cell layer of a GH primed cell. Thyroid hormone blocks the clonal expansion and stimulates chondrocyte maturation. IGF-I mRNA is primarily regulated by GH, and IGF-I is produced in several tissues such as the liver, muscle, fat and epiphyseal growth plates. However, IGF-I mRNA is also increased during compensatory growth of heart and kidneys and by estrogen in the Fallopian tube in the rat. Nutrition, i.e. energy from fat and carbohydrates and proteins, also influences the final height, but the cellular mechanism of action is not known. The aim of this article is to review hormonal action on longitudinal bone growth.

Animals↗
PubMed1993

Growth hormone-receptor messenger RNA in the rat ovary: regulation and localization.

The results of several reports indicate that GH can modulate ovarian function. In the present study, the expression of the growth hormone-receptor (GH-R) mRNA was studied in the rat ovary using an RNA probe corresponding to a part of the extracellular domain of the GH-R. The probe hybridized to two major transcripts with estimated sizes of 4.0 kb and 1.2 kb in RNA extracted from liver and ovary. Recently, these transcripts have been shown to encode the GH-R and the GH-binding protein (GH-BP). The ontogeny of the GH-R/GH-BP mRNA expression was studied using Northern blot analysis and a solution hybridization RNase protection assay. In the liver GH-R/GH-BP mRNA levels increased with age, while in the ovary, the levels decreased between 1 and 5 weeks of age. Hypophysectomy caused a decrease in GH-R/GH-BP gene expression in the ovary, an effect which could be partly reversed with a single injection of GH (2 mg/kg). No significant changes in the ovarian concentration of GH-R/GH-BP transcripts were seen during the estrus cycle. Using in situ hybridization GH-R/GH-BP transcripts were found to be most abundant in follicles. Northern blot analysis of RNA extracted from isolated granulosa cells and corpora lutea showed that both these compartments contained GH-R and GH-BP mRNA, although more abundant in granulosa cells. Immunoreactive GH-R was detected in granulosa cells of healthy follicles, corpus luteum, and in the germinal epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Establishment of a growth hormone responsive chondrogenic cell line from fetal rat tibia.

Reproducible effects of growth hormone (GH) on primary isolated cells in monolayer are highly dependent on the culture conditions and/or the fraction of GH responsive cells. To study the effect of GH at the cellular level, a homogenous cell line with both GH responsiveness and chondrogenic properties was established. Primary isolated cells from 18-day-old fetal rat tibia were subcultured using a strict protocol for passages (every third day and a seeding density of 15,000/cm2). Of six established cell lines, one fetal tibia cell line No. 5 (FTC 5) expressed adipogenic and chondrogenic properties at a low frequency. Cells from FTC 5 were subcultured in soft agar suspension with the addition of bovine GH (100 ng/ml). After 14 days in culture eight monoclonal cell lines were established from individual large colonies. Two subclones, FTC 5:3 and FTC 5:6, expressed a chondrogenic phenotype as demonstrated by chondrocyte foci, alcian blue staining and production of type II collagen. Further characterization of FTC 5:3 revealed specific binding of bovine GH with an affinity of 1.7 x 10(9) M-1, and approximately 7300 receptors/cell. Northern blot analysis of FTC 5:3 with a 32P-labeled RNA probe complementary to an extracellular part of the rat GH receptor, revealed two major labeled bands (4.0 and 1.2 kilobases). Both GH and insulin-like growth factor-I (IGF-I) stimulated 3H-thymidine uptake in FTC 5:3 (194 +/- 28% and 405 +/- 127% over control, respectively), while proteoglycan synthesis, as measured by [35S]sulphate uptake, was stimulated by IGF-I only (101 +/- 18% over control).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Treatment of adults with growth hormone (GH) deficiency with recombinant human GH.

In a double blind, cross-over placebo-controlled trial, we studied the effects of 26 weeks of replacement therapy with recombinant human GH on body composition, metabolic parameters, and well-being in 10 patients with adult-onset GH deficiency (GHD). All patients received appropriate thyroid, adrenal, and gonadal replacement therapy. The dose of recombinant human GH was 0.25-0.5 U/kg.week (0.013-0.026 mg/kg.day) and was administered sc daily at bedtime. One patient was withdrawn from the study because of edema and atrial fibrillation. Body composition was estimated with three independent methods: computed tomography, bioelectric impedance, and total body potassium combined with total body water assessments. The Comprehensive Psychological Rating Scale and the Symptom Check List-90 were used to assess any change in psychopathology. After 26 weeks of treatment, adipose tissue (AT) mass decreased 4.7 kg (P < 0.001). Subcutaneous AT decreased by an average of 13%, whereas visceral AT was reduced by 30%. Muscle volume increased by 2.5 kg (5%; P < 0.05). According to the four-compartment model derived from assessments of total body potassium and total body water, body cell mass and extracellular fluid volume increased significantly by 1.6 and 3.0 kg, whereas body fat decreased by 6.1 kg. Results obtained by the bioelectric impedance technique were similar. The mean (+/- SD) concentrations of insulin-like growth factor-I increased from 0.26 (0.06) at baseline to 2.56 (1.55) and 2.09 (1.03) kU/L after 6 and 26 weeks of treatment. Calcium and serum phosphate, osteocalcin, and procollagen-III concentrations were significantly higher, and intact PTH concentrations were reduced after 6 and 26 weeks of treatment, respectively. Total and free T3 concentrations were significantly increased after 6 and 26 weeks of treatment, whereas free T4 concentrations were reduced at 6 weeks, but after 26 weeks, free T4 concentrations had returned to pretreatment values. Finally, after 26 weeks of treatment, there was a decrease in the Comprehensive Psychological Rating Scale score (P < 0.05). The results show that GH replacement in GHD adults results in marked alterations in body composition, fat distribution, and bone and mineral metabolism and reduces psychiatric symptoms. Finally, we conclude that the observed beneficial effects of replacement therapy with GH are of sufficient magnitude to consider treatment of GHD adults.

Adipose Tissue↗
PubMed1992

Chronic elevation of cAMP levels induces changes in the adenylate cyclase system, opiate receptor sensitivity and levels of Gs-mRNA in cultured neurons.

Neurons in primary culture were treated (5 days) with the adenylate cyclase stimulator 10(-5) M forskolin. The basal adenylate cyclase was decreased by 57%. The acute stimulatory effect of forskolin was down-regulated by 48%. The inhibitory effects of the 3 opiate receptor agonists (mu, delta and kappa) were partly abolished. The abundance of mRNA encoding the stimulatory G-protein (Gs) was decreased prominently. The data indicate that the cAMP system in neuronal cells in primary culture is under dynamic regulation, possibly including altered Gs-protein gene expression. Furthermore, long-term forskolin treatment might induce increased proliferation in susceptible neural blast cells.

Adenylyl Cyclases↗
PubMed1992

Altered amounts of G-protein mRNA and cAMP accumulation after long-term opioid receptor stimulation of neurons in primary culture from the rat cerebral cortex.

Primary neuronal enriched cultures were incubated with mu (morphine, 10(-5) M), delta (DPDPE, 10(-6) M) and kappa (U-50,488H, 10(-5) M) receptor agonists for 5 days, respectively. Thereafter the acute inhibitory actions of mu, delta or kappa receptor agonists on forskolin stimulated cAMP accumulation was assayed. The effect of long term opioid treatment on the steady-state level of G-protein mRNA (G alpha s, G alpha i-1 and G alpha i-2) was analyzed using an RNAase protection hybridization assay. Incubation for 5 days with kappa receptor agonist resulted in an attenuated ability to decrease the accumulation of cAMP by kappa receptors, as well as mu and delta receptors, which was also observed after 5 days of incubation with the delta receptor agonist. Furthermore, the adenylate cyclase responsiveness to forskolin stimulation was markedly reduced in cultures treated with either delta or kappa receptor agonists. Five days of incubation with kappa receptor agonist resulted in an increase in the levels of G alpha s and G alpha i-2 mRNAs. No effects on the amounts of G alpha s mRNA, G alpha i-1 mRNA or G alpha i-2 mRNA were detected after 5 days of delta receptor stimulation. On the other hand, 5 days of mu receptor stimulation decreased the amounts of G alpha s, G alpha i-1 and G alpha i-2 mRNA. Incubation with kappa receptor agonist for 24 h resulted in a significant decrease in the forskolin-stimulated accumulation of cAMP. The stimulatory effect of forskolin was further decreased after 3 days incubation with kappa receptor agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Regulation of G-PROTEIN mRNA abundancy and cAMP accumulation after long-term opioid incubation in primary cultures of astroglia from the rat cerebral cortex.

Primary astroglial cultures were incubated with delta (10(-6) M DPDPE) or kappa (10(-5) M U-50,488H) receptor agonists for 5 days. Thereafter, the acute inhibitory actions of delta or kappa receptor agonists on forskolin stimulated cAMP accumulation were assayed. The G alpha s, G alpha i-1 and G alpha i-2 mRNA levels were quantified after 5 days of either delta or kappa receptor agonist treatment using a solution hybridization, RNase protection assay. Pronounced effects were observed after 5 days of kappa receptor agonist [10(-5) M U-50,488H] incubation. This treatment resulted in an attenuation in the acute inhibitory action of delta and kappa receptor agonists. Furthermore, a decreased stimulatory action of forskolin was seen. Similar effects were also seen after delta receptor stimulation. We also investigated the effects after 24 h and 3 days of incubation with the kappa receptor agonist (10(-5) M) U-50,488H. The 24 h incubation resulted in a decreased sensitivity to the acute inhibitory action of delta and kappa receptor agonists in the astroglial cultures. This effect was further accentuated after the 3 days of incubation with 10(-5) M U-50,488H. No significant change was seen in the basal accumulation of cAMP after incubation with the kappa agonist U-50,488H. However, after 5 days of incubation with the delta agonist DPDPE, a significantly increased basal accumulation of cAMP was seen in the astroglial cultures. After 5 days of delta or kappa agonist incubation, an increase in G alpha s mRNA level and a decrease in G alpha i-2 mRNA level was seen compared with controls. No statistically significant alterations in the amount of G alpha i-1 mRNA were seen. The data obtained in the present study indicate that the effects of long-term opioid treatment alters the sensitivity of glial cell opioid receptors. Furthermore, long term opioid treatment induces alterations in glial G-protein mRNA levels.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1992

Trophic effects of hypophyseal hormones on resistance vessels and the heart in normotensive and renal hypertensive rats.

UNLABELLED: Arterial pressure is an important determinant of cardiovascular structure and relates positively to it. The purpose of this study was to determine whether pituitary hormones influence the relation of pressure and structure. Male Sprague-Dawley rats, aged 5 weeks, were studied in three groups: the first underwent hypophysectomy; the second was hypophysectomized but received replacement therapy with growth hormone and thyroxine; the third served as controls. Four days later half of each group underwent unilateral renal artery clipping, the other half serving as normotensive controls. For 5 weeks estimates were made of systolic blood pressure, heart rate, body weight and plasma renin activity. Rats were then killed; left ventricular, kidney and adrenal weights were determined and, using hindquarter perfusion, estimates were made of resistance at maximal dilatation (reflecting inner radius), and of maximal pressor response (reflecting wall thickness). RESULTS: (1) Hypophysectomy in non-clipped rats reduced growth rate, systolic blood pressure and heart rate while plasma renin activity rose. As related to pressure and to body weight, resistance at maximal dilatation, maximal pressor response, left ventricular weight remained at the juvenile values of a 5-week-old rat. Hormone replacement restored values to those of control rats aged 11 weeks. (2) Clipping in the control group rats increased systolic blood pressure more than in hypophysectomized and growth hormone and thyroxine receiving hypophysectomized groups even though plasma renin activity remained higher in hypophysectomized than in control rats. Plasma renin activity was highest in hypophysectomized rats with highest pressure. (3) Systolic blood pressure related positively to left ventricle weight, resistance at maximal dilatation, maximal pressor response and calculated wall thickness to inner radius ratios in all groups. However, these regressions were all, like renal structural adaptation, considerably depressed in the hypophysectomized group. Hormone replacement restored the relation of structure and pressure towards that of control group rats. Thus, growth hormone and thyroxine influence maturation of the normal cardiovascular system and greatly enhance its structural upward resetting in hypertension.

Animals↗
PubMed1992

Roles of pulsatility and continuity of growth hormone (GH) administration in the regulation of hepatic GH-receptors, and circulating GH-binding protein and insulin-like growth factor-I.

GH secretion in the male rat is characterized by regular GH peaks of high amplitude, and their GH receptors and GH-binding protein (BP) are low. Female rats have a more continuous secretion, and their GH receptors and GH-BP are high. To determine how the pattern of GH delivery may affects the physiological responses to the hormone, hypophysectomized male rats were infused with human GH (1.5 U/kg.day) for 5 days through an implanted iv cannula in either a pulsatile manner (for 5 min every 3 h) or continuously. We then measured free and total (after MgCl2 treatment) somatogenic and lactogenic receptors in hepatic cell membranes, and GH-BP and immunoreactive insulin-like growth factor-I (IGF-I) in serum. The concentrations of occupied, but not free, somatogenic and lactogenic binding sites were higher 5 min after a 5-min infusion of human GH than 90 min after the infusion. Consequently, the total levels (free plus ligand binding) of somatogenic and lactogenic receptors were also higher 5 min after a GH pulse than after 90 min. The levels of circulating GH-BP were higher 90 min than 5 min after a GH pulse, and the serum IGF-I levels did not differ between these time points. The concentrations of free and total somatogenic and free lactogenic receptors in the liver, as well as GH-BP and IGF-I in circulation were higher and body weight gain was lower in rats given continuous GH infusion than after pulsatile infusions. It is concluded that the nature of GH-levels profile has a marked influence on the interrelationship of GH, GH receptors, GH-BP, serum IGF-I and growth, whereby the later is stimulated maximally by pulsatile GH-levels, while the receptor and GH-BP are enhanced maximally by continuous levels. The basis for this discrepancy may lay in the competitive power of GH-BP toward GH receptor binding. A pulsatile GH pattern induced cyclicity in the levels of hepatic cell membrane GH receptors and circulating GH-BP. It is suggested that these factors are regulated in a similar way by the plasma GH pattern in pituitary intact rats.

Animals↗
PubMed1992

Effect of growth hormone and insulin-like growth factor-I on DNA synthesis and matrix production in rat epiphyseal chondrocytes in monolayer culture.

The influence of various culture conditions was studied on the effect of GH and insulin-like growth factor-I (IGF-I) on DNA and matrix synthesis in epiphyseal rat chondrocytes in monolayer culture. Chondrocytes from enzymatically digested rat tibia epiphyseal growth plates were seeded in 48-well culture plates and precultured for 10 days in Ham's F-12 medium supplemented with 1% (v/v) newborn calf serum and 1% (v/v) of a serum substitute. After preculture, the medium was changed to Ham's F-12 medium supplemented with 1% serum from hypophysectomized rats, and the effect of GH and IGF-I on DNA synthesis ([3H]thymidine incorporation) and matrix production ([35S]sulphate uptake) was studied during an additional 96-h culture period. Isotopes were present during the last 24 h of culture. Both hGH and IGF-I stimulated DNA synthesis in a dose-dependent manner. A maximal effect of GH was seen at a concentration of 25 micrograms/l (60 +/- 11% stimulation over control) and for IGF-I at 10 micrograms/l (162 +/- 12%). The stimulatory effects of the same concentrations of human GH (hGH) and IGF-I on [35S]sulphate uptake were 135 +/- 25 and 320 +/- 42% respectively. In-vitro pulse labelling revealed that GH did not produce a response during the first 3 days of culture (after addition of GH) but was effective during days 4 and 5 of culture. In contrast, IGF-I was effective throughout the culture period. Pretreatment of cells with GH or IGF-I for 2.5 days showed that GH but not IGF-I produced a sustained effect on [3H]thymidine uptake. In order to study the influence of cell density on the effect of GH and IGF-I on DNA synthesis, the effect of added peptides was evaluated after different preculture periods (5-15 days). A maximal stimulatory effect of hGH was seen at a cell density of 150,000-300,000 cells/cm2. GH had no significant effect at a low (less than 100,000 cells/cm2) or a high (greater than 400,000 cells/cm2) cell density. The magnitude of the stimulatory effect of IGF-I was the same at densities between 10,000 and 250,000 cells/cm2, but was reduced at higher cell densities (over 250,000 cells/cm2). Chondrogenic properties of cells that had been cultured for 15 days were verified in vitro by positive alcian blue staining and identification of type II collagen, and in vivo by development of cartilage nodules in nude mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Induction of mammary adenocarcinomas in metallothionein promoter-human growth hormone transgenic mice.

To develop transgenic mice, a mouse metallothionein promoter-human growth hormone (Mt-hGH) gene fragment was injected into the pronucleus of C57BI x DBA/2J F2 one-cell embryos. Six founder animals grew larger (1.3-2.2 times) than littermate controls and had higher levels of hGH in plasma (4.6-279 mU/l). At 27-43 weeks of age, 3 of the 4 female transgenic founders developed malignant papillary adenocarcinomas of mammary origin. One of the male transgenic founders was successfully mated and 2 of 3 female transgenic offspring developed mammary tumors. Forty-two female mice with the same genetic background as the transgenic animals and older than 43 weeks served as controls. No palpable tumor was found in this group. Five of the control animals were killed and examined histologically, revealing only normal mammary tissue. Earlier studies have shown that GH is important for growth and development of the mammary gland. Our study suggests that markedly elevated endogenous levels of GH cause mammary carcinoma in a specific strain of transgenic mice. The present animal model might be useful for studying molecular mechanisms that are involved in the development of hormonally induced mammary tumors.

Adenocarcinoma↗
PubMed1991

Regulation of cartilage growth by growth hormone and insulin-like growth factor I.

A number of studies have shown that growth hormone (GH) and insulin-like growth factor-I (IGF-I) have important regulatory roles for skeletal growth. However, it has been a matter of controversy whether GH acts directly on cells in the growth plate or if the growth-promoting effects of GH are mediated by liver-derived (endocrine-acting) IGF-I. With the recognition that GH regulates the production of IGF-I in multiple extra-hepatic tissues, autocrine and paracrine functions of IGF-I have been suggested as important components of GH action. This review focuses on recent developments in our understanding of the cellular mechanisms by which GH promotes longitudinal bone growth and the inter-relationship between GH and IGF-I in the growth plate.

Animals↗
PubMed1991

Expression and physiological significance of growth hormone receptors and growth hormone binding proteins in rat and man.

The molecular structure of the GH receptor has recently been characterized and the receptor identified as a member of a new receptor superfamily that includes the prolactin receptor and several cytokine receptors. No obvious signal transducing domain has been identified on any of these related receptors. One possible signalling mechanism involves receptor interaction with other membrane-associated proteins that function as mediators of signal transduction. Whether such a mechanism is involved in signal transduction of the GH receptor is not known. Another common feature of these receptors is the presence of soluble forms such as the GHBP. The functions of these proteins in the circulation and at the level of the target cell remain to be resolved.

Animals↗
PubMed1990

Expression of the growth hormone-binding protein messenger RNA in the liver and extrahepatic tissues in the rat: co-expression with the growth hormone receptor.

A cDNA encoding a growth hormone-binding protein (GH-BP) was recently cloned from mouse and rat liver. The GH-BP in these species is identical to the extracellular part of the GH receptor (GH-R) with the transmembrane and intracellular domain substituted for a hydrophilic tail. In the present study the expression of the GH-BP and GH-R was studied in rat liver and extrahepatic tissues. Specific transcripts with estimated sizes of 1.2 kb (GH-BP) and 4.0 kb (GH-R) were found in the liver from both sexes. The expression of GH-BP increased with age up to puberty suggesting that it is developmentally regulated in a similar manner as GH-R. GH-BP mRNA was found in all extrahepatic tissues examined that contained GH-R mRNA. The ratio between the 1.2 kb and 4.0 kb transcripts varied between tissues indicating that GH-R and GH-BP transcripts may be separately regulated. The co-expression of GH-BP and GH-R suggests a functional role for the GH-BP in the local regulation of GH action.

Age Factors↗
PubMed1990

Growth hormone regulation of the growth hormone receptor mRNA in cultured rat epiphyseal chondrocytes.

This study was designed to investigate whether growth hormone (GH) influences the expression of its own receptor in chondrocytes. To investigate this possibility GH-receptor mRNA was measured in cultured rat epiphyseal chondrocytes in the absence or presence of GH under various experimental conditions. Chondrocytes were isolated enzymatically from epiphyseal growth plates of the proximal tibia of 20-day-old male rats and cultured in monolayer in Ham's F-12 medium supplemented with 10% calf serum and 1% of a serum substitute. The cells were seeded at various densities (100,000-1,000,000 cells per flask) and cultured for 14 days. Subsequently, the calf serum-containing medium and the cells cultured for various periods of time (0-24 h) before total nucleic acid preparation. GH-receptor mRNA was measured with a solution hybridization technique using [35S]UTP-labeled RNA growth hormone receptor cloned from rat liver cDNA. Human GH (hGH; 50 ng/ml) increased GH-receptor mRNA after 3 h and maximal levels were seen 12 h after GH addition. This effect of hGH was time and dose dependent with a significant effect of hGH at a concentration of 0.5 ng/ml and a maximal effect at 50 ng/ml. The hGH-stimulated increase of GH-receptor mRNA was completely blocked by actinomycin-C1 (1.0-0.1 micrograms/ml), while cycloheximide (10 micrograms/ml) only slightly counteracted the hGH effect. Rat and human GH were equally potent, and ovine prolactin was effective at 500 ng/ml but not 5 and 50 ng/ml. A high dose of insulin-like growth factor-I (IGF-I; 1 microgram/ml) caused a small stimulatory effect and addition of 10% calf serum caused a marked increase in GH-receptor mRNA. The level of GH receptor mRNA after 14 days of culture was inversely proportional to the cell density at the start of culture. These results show that GH specifically regulates mRNA levels for its own receptor in rat epiphyseal chondrocytes by interacting with somatogenic binding sites. These findings also suggest a transcription-dependent regulatory system between the GH-receptor and the GH-receptor gene.

Animals↗