Growth hormone and insulin-like growth factor-I act together and independently when regulating growth in vertebral and muscle tissue of atlantic salmon postsmolts

Aiming to elucidate the role of GH and IGF-I with regard to vertebral and white muscle growth, gene expression of the GH and IGF-I receptors (ghr and igf-Ir, respectively) and local IGF-I (igf-I) were analyzed during spring growth (January-June) in Atlantic salmon postsmolts. One group of fish was reared under natural light (NL), while one group was reared under continuous light (LL). Growth rate of fork length was higher in the LL group for a short period after onset of continuous light (LL: 0.50+/-0.02 mm day(-1), NL: 0.43+/-0.01 mm day(-1)) and for a longer period at the end of the experiment in June (LL: 1.18+/-0.06 mm day(-1), NL: 0.75+/-0.02 mm day(-1)). Likewise, growth rate in length of vertebra No. 40 in the LL group was higher than in the NL group the first period after onset of light (LL: 0.015+/-0.002 mm day(-1), NL: 0.008+/-0.001 mm day(-1)). Plasma GH levels peaked in late February and were higher in the LL group than in the NL group (LL: 7.27+/-0.61 ng ml(-1), NL: 2.60+/-0.50 ng ml(-1)), whereas plasma IGF-I levels peaked in early February and were unaffected by photoperiod. ghr expression was upregulated in late February in liver (12-fold), white muscle (6-fold) and vertebral tissue (3-fold) and higher in the LL group than in the NL group (2-fold) in vertebral tissue in late March. White muscle expression of igf-I and igf-Ir decreased from initial levels throughout the experiment. Hepatic gene expression of igf-I doubled in both groups in late February, followed by a 4-fold upregulation in June in the LL group only. Vertebral tissue expression of igf-I (4-fold) and igf-Ir (6-fold) increased in May and were unaffected by photoperiod. One exception was a smaller upregulation of igf-I (2-fold) in the LL group in early February. In conclusion, GH appears to have an initial role in stimulating vertebral growth, while IGF-I seems to stimulate growth during late spring. It is suggested that local IGF-I acts as a paracrine agent, evaluated from the concurrent upregulation of igf-I and igf-Ir. The upregulation of ghr in white muscle tissue, concurrent with a downregulation of muscle igf-I and igf-Ir, indicate that GH stimulated growth or metabolism independent of IGF-I.     

Endocrine effects of growth hormone overexpression in transgenic coho salmon

Non-transgenic (wild-type) coho salmon (Oncorhynchus kisutch), growth hormone (GH) transgenic salmon (with highly elevated growth rates), and GH transgenic salmon pair fed a non-transgenic ration level (and thus growing at the non-transgenic rate) were examined for plasma hormone concentrations, and liver, muscle, hypothalamus, telencephalon, and pituitary mRNA levels. GH transgenic salmon exhibited increased plasma GH levels, and enhanced liver, muscle and hypothalamic GH mRNA levels. Insulin-like growth factor-I (IGF-I) in plasma, and growth hormone receptor (GHR) and IGF-I mRNA levels in liver and muscle, were higher in fully fed transgenic than non-transgenic fish. GHR mRNA levels in transgenic fish were unaffected by ration-restriction, whereas plasma GH was increased and plasma IGF-I and liver IGF-I mRNA were decreased to wild-type levels. These data reveal that strong nutritional modulation of IGF-I production remains even in the presence of constitutive ectopic GH expression in these transgenic fish. Liver GHR membrane protein levels were not different from controls, whereas, in muscle, GHR levels were elevated approximately 5-fold in transgenic fish. Paracrine stimulation of IGF-I by ectopic GH production in non-pituitary tissues is suggested by increased basal cartilage sulphation observed in the transgenic salmon. Levels of mRNA for growth hormone-releasing hormone (GHRH) and cholecystokinin (CCK) did not differ between groups. Despite its role in appetite stimulation, neuropeptide Y (NPY) mRNA was not found to be elevated in transgenic groups.     

Endocrine systems in juvenile anadromous and landlocked Atlantic salmon (Salmo salar): seasonal development and seawater acclimation

The present study compares developmental changes in plasma levels of growth hormone (GH), insulin-like growth factor I (IGF-I) and cortisol, and mRNA levels of their receptors and the prolactin receptor (PRLR) in the gill of anadromous and landlocked Atlantic salmon during the spring parr-smolt transformation (smoltification) period and following four days and one month seawater (SW) acclimation. Plasma GH and gill GH receptor (GHR) mRNA levels increased continuously during the spring smoltification period in the anadromous, but not in landlocked salmon. There were no differences in plasma IGF-I levels between strains, or any increase during smoltification. Gill IGF-I and IGF-I receptor (IGF-IR) mRNA levels increased in anadromous salmon during smoltification, with no changes observed in landlocked fish. Gill PRLR mRNA levels remained stable in both strains during spring. Plasma cortisol levels in anadromous salmon increased 5-fold in May and June, but not in landlocked salmon. Gill glucocorticoid receptor (GR) mRNA levels were elevated in both strains at the time of peak smoltification in anadromous salmon, while mineralocorticoid receptor (MR) mRNA levels remained stable. Only anadromous salmon showed an increase of gill 11beta-hydroxysteroid dehydrogenase type-2 (11beta-HSD2) mRNA levels in May. GH and gill GHR mRNA levels increased in both strains following four days of SW exposure in mid-May, whereas only the anadromous salmon displayed elevated plasma GH and GHR mRNA after one month in SW. Plasma IGF-I increased after four days in SW in both strains, decreasing in both strains after one month in SW. Gill IGF-I mRNA levels were only increased in landlocked salmon after 4days in SW. Gill IGF-IR mRNA levels in SW did not differ from FW levels in either strain. Gill PRLR mRNA did not change after four days of SW exposure, and decreased in both strains after one month in SW. Plasma cortisol levels did not change following SW exposure in either strain. Gill GR, 11beta-HSD2 and MR mRNA levels increased after four days in SW in both strains, whereas only the anadromous strain maintained elevated gill GR and 11beta-HSD2 mRNA levels after one month in SW. The results indicate that hormones and receptors of the GH and cortisol axes are present at significantly lower levels during spring development and SW acclimation in landlocked relative to anadromous salmon. These findings suggest that attenuation of GH and cortisol axes may, at least partially, result in reduced preparatory upregulation of key gill ion-secretory proteins, possibly a result of reduced selection pressure for marine adaptations in landlocked salmon.     

Multiple molecular effect pathways of an environmental oestrogen in fish

Complex interrelationships in the signalling of oestrogenic effects mean that environmental oestrogens present in the aquatic environment have the potential to disrupt physiological function in fish in a more complex manner than portrayed in the present literature. Taking a broader approach to investigate the possible effect pathways and the likely consequences of environmental oestrogen exposure in fish, the effects of 17beta-oestradiol (E(2)) were studied on the expression of a suite of genes which interact to mediate growth, development and thyroid and interrenal function (growth hormone GH (gh), GH receptor (ghr ), insulin-like growth factor (IGF-I) (igf1), IGF-I receptor (igf1r ), thyroid hormone receptors-alpha (thra) and -beta (thrb) and glucocorticoid receptor (gr )) together with the expression analyses of sex-steroid receptors and ten other genes centrally involved in sexual development and reproduction in fathead minnow (fhm; Pimephales promelas). Exposure of adult fhm to 35 ng E(2)/l for 14 days induced classic oestrogen biomarker responses (hepatic oestrogen receptor 1 and plasma vitellogenin), and impacted on the reproductive axis, feminising "male" steroidogenic enzyme expression profiles and suppressing genes involved in testis differentiation. However, E(2) also triggered a cascade of responses for gh, ghr, igf1, igf1r, thra, thrb and gr in the pituitary, brain, liver, gonad and gill, with potential consequences for the functioning of many physiological processes, not just reproduction. Molecular responses to E(2) were complex, with most genes showing differential responses between tissues and sexes. For example, igf1 expression increased in brain but decreased in gill on exposure to E(2), and responded in an opposite way in males compared with females in liver, gonad and pituitary. These findings demonstrate the importance of developing a deeper understanding of the endocrine interactions for unravelling the mechanisms of environmental oestrogen action and predicting the likely health consequences.     

Growth and endocrine effects of recombinant bovine growth hormone treatment in non-transgenic and growth hormone transgenic coho salmon

To examine the relative growth, endocrine, and gene expression effects of growth hormone (GH) transgenesis vs. GH protein treatment, wild-type non-transgenic and GH transgenic coho salmon were treated with a sustained-release formulation of recombinant bovine GH (bGH; Posilac). Fish size, specific growth rate (SGR), and condition factor (CF) were monitored for 14 weeks, after which endocrine parameters were measured. Transgenic fish had much higher growth, SGR and CF than non-transgenic fish, and bGH injection significantly increased weight and SGR in non-transgenic but not transgenic fish. Plasma salmon GH concentrations decreased with bGH treatment in non-transgenic but not in transgenic fish where levels were similar to controls. Higher GH mRNA levels were detected in transgenic muscle and liver but no differences were observed in GH receptor (GHR) mRNA levels. In non-transgenic pituitary, GH and GHR mRNA levels per mg pituitary decreased with bGH dose to levels seen in transgenic salmon. Plasma IGF-I was elevated with bGH dose only in non-transgenic fish, while transgenic fish maintained an elevated level of IGF-I with or without bGH treatment. A similar trend was seen for liver IGF-I mRNA levels. Thus, bGH treatment increased fish growth and influenced feedback on endocrine parameters in non-transgenic but not in transgenic fish. A lack of further growth stimulation of GH transgenic fish suggests that these fish are experiencing maximal growth stimulation via GH pathways.     

A quantitative real-time RT-PCR assay for salmon IGF-I mRNA, and its application in the study of GH regulation of IGF-I gene expression in primary culture of salmon hepatocytes

The hormone insulin-like growth factor-I (IGF-I) regulates vertebrate growth. The liver produces most circulating IGF-I, under the control of pituitary growth hormone (GH) and nutritional status. To study the regulation of liver IGF-I production in salmon, we established a primary hepatocyte culture system and developed a TaqMan quantitative real-time RT-PCR assay for salmon IGF-I gene expression. A portion of the coho salmon acidic ribosomal phosphoprotein P0 (ARP) cDNA was sequenced for use as a reference gene. A systematic bias across the 96 well PCR plate was discovered in an initial IGF-I assay, which was corrected when the assay was redesigned. IGF-I mRNA levels measured with the validated assay correlated well with levels measured with an RNase protection assay, and were highest in liver compared with other tissues. We examined the time course of hepatocyte IGF-I gene expression over 48 h in culture, the response to a range of GH concentrations in hepatocytes from fed and fasted fish, and potential effects of variation in IGF-I in the medium. IGF-I gene expression decreased over time in culture in hepatocytes in plain medium, and in cells treated with 5 nM GH with or without a combination of metabolic hormones (1 microM insulin, 100 nM triiodothyronine, and 0.1 nM dexamethasone). GH stimulated IGF-I gene expression at all time points. In cells treated with GH plus metabolic hormones, IGF-I gene expression was intermediate between the controls and GH alone. Increasing concentrations of GH resulted in biphasic IGF-I gene expression response curves in cells from fed and fasted fish, with the threshold for stimulation from 0.5 to 2.5 nM GH, maximal response from 5 to 50 nM, and a reduced response at 500 nM. Medium IGF-I (5 nM) did not affect basal or GH stimulated IGF-I gene expression. This study shows that primary hepatocyte culture and the TaqMan IGF-I assay can be used to study the regulation of hepatic IGF-I gene expression in salmon, and provides the first evidence of a biphasic response to GH concentration in fish hepatocyte culture.     

Regulation of hepatic growth hormone receptors in coho salmon (Oncorhynchus kisutch).

Factors potentially regulating hepatic growth hormone (GH) receptors in coho salmon (Oncorhynchus kisutch) have been investigated. From December to June of the first year, relative changes in hepatic 125I-sGH binding and 35SO4 incorporation by ceratobranchial cartilage were similar. Stunted salmon, which in seawater have elevated plasma GH yet fail to grow, showed lower hepatic 125I-sGH binding than did normally growing seawater salmon. However, MgCl2 treatment of stunts' membranes to reveal total specific binding of 125I-sGH indicated receptor occupation by endogenous sGH. Total specific 125I-sGH binding was low in seawater stunts and remained low if these fish remained unfed after return to fresh water, but increased approximately twofold upon feeding. Total specific binding in fasted salmon in fresh water showed a trend toward decreased levels by 1 week; by 3 weeks, binding was 40% lower than in fed fish. There was a positive correlation (r = 0.600) between condition factor and total specific binding in fed and fasted salmon in fresh water. Two weeks after hypophysectomy total specific binding was 50% lower than in sham-operated control salmon, indicating pituitary regulation of GH receptors. GH treatment reduced both free and total 125I-sGH binding in salmon examined 24 hr after treatment. Treatment with recombinant bovine insulin-like growth factor I, thyroxine, or cortisol did not affect free 125I-sGH binding. Both the pituitary and nutrition appear to be prime regulators of hepatic GH receptors in coho salmon.     

Time course of the GH/IGF axis response to fasting and increased ration in chinook salmon (Oncorhynchus tshawytscha)

Body growth in vertebrates is chiefly regulated by the GH/IGF axis. Pituitary growth hormone (GH) stimulates liver insulin-like growth factor-I (IGF-I) production. During fasting, plasma IGF-I levels decline due to the development of liver GH resistance, while GH levels generally increase. In mammals, decreased insulin during fasting is thought to cause liver GH resistance. However, the sequence of events in the GH/IGF axis response to fasting is not well characterized, especially in non-mammalian vertebrates. We assessed the time course of the GH/IGF axis response to fasting and increased ration in chinook salmon. Fish were placed on Fasting, Increased, or Control rations, and sampled daily for 4 days and at more widely spaced intervals through 29 days. Plasma IGF-I, GH, insulin, and 41 kDa IGF binding protein (putative salmon IGFBP-3), and liver IGF-I gene expression were measured. Control and Increased ration fish did not differ strongly. Plasma IGF-I and 41 kDa IGFBP were significantly lower in Fasted versus Control fish from day 4 onward, and liver IGF-I gene expression was significantly lower from day 6 onward. Liver IGF-I gene expression and plasma IGF-I levels were correlated. Plasma insulin was lower in Fasted fish from day 6 onward. There was a trend toward increased GH in Fasted fish on days 1-2, and GH was significantly increased Fasted fish from day 3 onward. Fasted GH first increased (days 1-3) to a plateau of 10-20 ng/ml (days 4-12) and then increased dramatically (days 15-29), suggesting that the GH response to fasting had three phases. The early increase in GH, followed by the decrease in plasma IGF-I after 4 days, suggests that GH resistance developed within 4 days.     

Effects of fasting on growth hormone, growth hormone receptor, and insulin-like growth factor-I axis in seawater-acclimated tilapia, Oreochromis mossambicus

Effects of fasting on the growth hormone (GH)--growth hormone receptor (GHR)-insulin-like growth factor-I (IGF-I) axis were characterized in seawater-acclimated tilapia (Oreochromis mossambicus). Fasting for 4 weeks resulted in significant reductions in body weight and specific growth rate. Plasma GH and pituitary GH mRNA levels were significantly elevated in fasted fish, whereas significant reductions were observed in plasma IGF-I and hepatic IGF-I mRNA levels. There was a significant negative correlation between plasma levels of GH and IGF-I in the fasted fish. No effect of fasting was observed on hepatic GHR mRNA levels. Plasma glucose levels were reduced significantly in fasted fish. The fact that fasting elicited increases in GH and decreases in IGF-I production without affecting GHR expression indicates a possible development of GH resistance.     

Response of the somatotropic axis of juvenile coho salmon to alterations in plane of nutrition with an analysis of the relationships among growth rate and circulating IGF-I and 41 kDa IGFBP

The effect of different feeding levels on plasma levels of insulin-like growth factor-I (IGF-I), 41 kDa insulin-like growth factor binding protein (41 kDa IGFBP), and growth hormone (GH) were assessed in post-smolt coho salmon. Fish were fed at either stable (1 and 2% body weight/day) or varying (1-0.5-1%, 2-0.5-2% body weight/day) feeding rates and plasma was sampled from 10 fish/treatment at 2-3 week intervals over five dates from June to September, resulting in a total of 200 samples. Fish fed at higher rates grew faster and had higher plasma IGF-I and 41 kDa IGFBP levels. Plasma GH levels were variable but generally showed an inverse relationship to feeding rate. Both plasma IGF-I and 41 kDa IGFBP increased seasonally, average IGF-I levels doubled from June to September, regardless of feeding rate. On any one date both IGF-I and 41 kDa IGFBP were highly related to growth rate with regression coefficients ranging from 0.36 to 0.68 (IGF-I) and from 0.33 to 0.70 (41 kDa IGFBP). No relationship was found between IGF-I:41 kDa IGFBP ratio and individual growth rate. Overall, both feeding rate and date were important in explaining variation in IGF-I and 41 kDa IGFBP levels.     

Free and protein-bound insulin-like growth factor-I (IGF-I) and IGF-binding proteins in plasma of coho salmon, Oncorhynchus kisutch.

Total and free insulin-like growth factor-I (IGF-I) levels were quantified in plasma from growth hormone (GH)-treated and fasted coho salmon. Total IGF-I was measured by radioimmunoassay after acid-ethanol extraction and free IGF-I was separated from protein-bound IGF-I using ultrafiltration by centrifugation. Total and free IGF-I increased in plasma after GH treatment and decreased after fasting. The level of free IGF-I, however, was maintained at approximately 0.3% in both experiments. Unsaturated binding activity in plasma for IGF-I was assessed by incubation with (125)I-recombinant salmon IGF-I ((125)I-sIGF-I). Although there was no difference in binding activity between GH-treated and control fish, fasted fish showed higher binding activity than did fed fish, suggesting induction of unsaturated binding protein by fasting. IGF-binding protein (IGFBP) bands were observed in plasma of coho salmon by Western ligand blotting using (125)I-sIGF-I. A low-molecular-weight (22 kDa) band was clear in fasted fish but not detectable in fed fish. The IGFBP band, which has molecular weight similar to that of human IGFBP-3 (41 kDa), was more intense in GH-treated fish than in controls. The molecular distribution of IGF-I in plasma was examined by gel filtration under neutral conditions. Most IGF-I was eluted around 40 kDa. This result suggests that the major form of bound IGF-I in the circulation of coho salmon may be in a 40-kDa binary complex rather than in a 150-kDa ternary complex, as in mammals.     

Lysine intake affects gene expression of anabolic hormones in Atlantic salmon, Salmo salar

Nutritional factors influence regulation of the growth hormone (GH) and the insulin-like growth factor (IGF) system in fish, but so far there are no published studies describing how single indispensable amino acids influence these systems. Therefore, the present study aimed to test whether lysine (Lys) intake at low (LL=2.85 g/16 gN), medium (ML=4.91 g/16 gN) and high levels (HL=9.19 g/16 gN) affected the expression of genes related to the GH-IGF system (i.e. GH receptor, GH-R, IGF-I, IGF-II, IGF binding protein 1, IGFBP-1, IGF-I receptor IGF-IR) in Atlantic salmon during seawater growth phase. Salmon fed the HL diet significantly up-regulated hepatic IGF-I mRNA level by a factor of 2.2 as compared to those with medium Lys intake. In addition a significant up-regulation of 2.7-fold in muscle IGF-II mRNA was present. Low Lys intake decreased the nitrogen deposition and muscle protein accretion in fish and significantly down-regulated hepatic IGFBP-1 as well as muscle GH-R and IGF-II, as compared to those fed the ML diet. mRNA of IGF-IR on the other hand was not affected by Lys intake. High Lys intake resulted in a 7-fold up-regulation of muscle IGF-II mRNA level as compared to low Lys intake, and thus might be an important local anabolic regulator in fast muscle tissue. The single indispensable amino acid Lys indeed affected signalling through the genes of IGF-I, IGFBP-1 in hepatic tissue and GH-R, IGF-II in fast muscle in Atlantic salmon. Concomitantly the higher Lys intake increased nitrogen deposition to a certain level.     

Growth hormone endocrinology of Atlantic salmon (Salmo salar): pituitary gene expression, hormone storage, secretion and plasma levels during parr-smolt transformation.

A number of studies on the Atlantic salmon (Salmo salar), have reported changes in plasma GH during parr-smolt transformation, but there is a lack of information about the endocrinology of the GH system during this process. In order to elucidate the mechanisms underlying these changes in plasma GH levels during the parr-smolt transformation of Atlantic salmon, GH mRNA expression in the pituitary was studied together with total pituitary GH content, in vitro GH secretion rate and plasma GH and IGF-I levels. Atlantic salmon were kept in outside tanks, under natural condition from early February until late June. Approximately three times a month fish were killed and pituitaries and blood were sampled for investigation. Further, pituitaries were moved to the laboratory for in vitro GH secretion studies. The results show that the GH system is first activated by an increase in GH secretion rate, which leads to an increase in plasma GH levels and causes a drop in the total GH content of the pituitary. This drop in pituitary GH content is later reversed by an increased GH synthesis seen as an increase in GH mRNA expression. Maximal activation of the GH system is seen to occur in early May, when plasma IGF-I levels reach highest levels, after which a certain deactivation of the GH system takes place. The data show that plasma levels of GH are to a large extent regulated by the secretion rate from the pituitary, although changes in the GH clearance rate are also likely to take place and influence the plasma GH levels. The study further underlines the significant role that the GH-IGF-I axis plays in the parr-smolt transformation of the Atlantic salmon.     

Resolving the growth-promoting and metabolic effects of growth hormone: Differential regulation of GH-IGF-I system components

Growth hormone regulates numerous processes in vertebrates including growth promotion and lipid mobilization. During periods of food deprivation, growth is arrested yet lipid depletion is promoted. In this study, we used rainbow trout on different nutritional regimens to examine the regulation of growth hormone (GH)-insulin-like growth factor-I (IGF-I) system elements in order to resolve the growth-promoting and lipid catabolic actions of GH. Fish fasted for 2 or 6 weeks displayed significantly reduced growth compared to their fed counterparts despite elevated plasma GH, while refeeding for 2 weeks following 4 weeks of fasting partially restored growth and lowered plasma GH. Fish fasted for 6 weeks also exhausted their mesenteric adipose tissue reserves. Sensitivity to GH in the liver was reduced in fasting fish as evidenced by reduced expression of GH receptor type 1 (GHR 1) and GHR 2 mRNAs and by reduced (125)I-GH binding capacity. Expression of GHR 1 and GHR 2 mRNAs also was reduced in the gill of fasted fish. In adipose tissue, however, sensitivity to GH, as indicated by GHR 1 expression and by (125)I-GH binding capacity, increased after 6 weeks of fasting in concert with the observed lipid depletion. Fasting-associated growth retardation was accompanied by reduced expression of total IGF-I mRNA in the liver, adipose and gill, and by reduced plasma levels of IGF-I. Sensitivity to IGF-I was reduced in the gill of fasted fish as indicated by reduced expression of type 1 IGF-I receptor (IGFR 1A and IGFR 1B) mRNAs. By contrast, fasting did not affect expression of IGFR 1 mRNAs or (125)I-IGF-I binding in skeletal muscle and increased expression of IGFR 1 mRNAs and (125)I-IGF-I binding in cardiac muscle. These results indicate that nutritional state differentially regulates GH-IGF-I system components in a tissue-specific manner and that such alterations disable the growth-promoting actions of GH and promote the lipid-mobilizing actions of the hormone.     

Growth hormone gene expression in canine normal growth plates and spontaneous osteosarcoma

The indirect growth-promoting action of pituitary-derived growth hormone (GH) on skeletal growth is thought to be mediated by systemically released insulin-like growth factor-I (IGF-I) and by locally produced IGF-I. The aim of the present study was to document whether GH is expressed locally in canine bone and spontaneous osteosarcoma. Using RT-PCR the expression of GH mRNA was demonstrated in the metaphyseal, but not in the majority of epiphyseal ends of the canine growth plate. GH mRNA was also present in 25% of the canine osteosarcoma specimens. The expression of GH mRNA in predominantly active osteoid forming areas was associated with the presence of immunoreactive GH in osteoblasts, as shown by immunohistochemistry. It is concluded that locally produced GH is involved in osteoid formation and may play a role in the growth of neoplastic bone lesions in the dog.     

Developmental expression of hepatic growth hormone receptor and insulin-like growth factor-I mRNA in the chicken.

We have examined the ontogeny of expression of growth hormone (GH) receptor (GHR) and insulin-like growth factor-I (IGF-I) mRNA in chicken liver from day 13 of incubation until 31 weeks of age. The profiles of GHR and IGF-I mRNA levels were compared to developmental changes in body weight and plasma levels of GH and IGF-I. In the embryo, hepatic GHR mRNA was not detectable until day 15, highest on days 17 and 19, and then declined at hatching (day 21). Following an initial 2-week delay after hatching, there was a progressive increase in hepatic GHR mRNA which continued after the birds reached mature body weight. Plasma GH reached peak levels at 3-4 weeks of age and then fell sharply until maintenance of a low basal level after 10 weeks of age. Thus, there appears to be a strong inverse relationship between expression of the GHR and basal plasma GH levels in the prepubertal chicken. Although IGF-I mRNA was undetectable in embryonic liver by Northern blot analysis, there is a good correlation between expression of hepatic IGF-I mRNA and the plasma IGF-I profile during post-hatching development in the chicken. The highest levels of IGF-I mRNA were reached at 4 weeks of age which was followed by a slow decline to the basal levels maintained after 10 weeks of age. It appears that the decline in plasma IGF-I lags considerably behind the sharp fall in plasma GH levels and expression of hepatic IGF-I mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Androgen effects on plasma GH, IGF-I, and 41-kDa IGFBP in coho salmon (Oncorhynchus kisutch)

Among many species of salmonids, fast growing fish mature earlier than slow growing fish, and maturing males grow faster than non-maturing ones. To study the potential endocrine basis for this reciprocal relationship we examined the in vivo effects of the androgens, testosterone (T) and 11-ketotestosterone (11-KT), on plasma growth hormone (GH), insulin-like growth factor-I (IGF-I) and 41-kDa IGF binding protein (41-kDa IGFBP) (putative IGFBP-3) in coho salmon, Oncorhynchus kisutch. Immature male and female, two-year old fish (avg. wt. 31.7 +/- 0.63 g) were injected with coconut oil containing T or 11-KT at a dose of 0.1, 0.25, or 1 microg/g body weight. Blood samples were taken 1 and 2 weeks postinjection, and analyzed by immunoassay for T, 11-KT, GH, IGF-I, and 41-kDa IGFBP. Steroid treatments elevated the plasma T and 11-KT levels to physiological ranges typical of maturing fish. Plasma IGF-I and 41-kDa IGFBP levels increased in response to both T and 11-KT in a significant and dose-dependent manner after 1 and 2 weeks, but GH levels were not altered. These data suggest that during reproductive maturation, in addition to the previously demonstrated effects of the IGFs on steroidogenesis, the gonadal steroids may in turn play a significant role in regulating IGF-I and its binding proteins in fish. The interaction between the reproductive and growth axes may provide a regulatory mechanism for bringing about the dimorphic growth patterns observed between maturing and non-maturing salmonids and other species of fish.