Upregulation of GH receptor and GH binding protein during pregnancy in the GH deficient rat

Gargosky, Sharron; Breier, Bernhard H.; Borski, Russell J.; Mulcahy, John J.; Barnard, Ross

doi:10.1007/bf02935686

Cited by 6 publications

(6 citation statements)

References 25 publications

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“…The GHBP levels reported in this study were rather low for pregnant rats, as circulating GHBP levels normally increase during pregnancy (Barnard & Waters 1997). A 5-fold increase in GHBP levels has previously been observed in pregnant rats compared with non-pregnant rats (R Barnard, S M Woodall & B H Breier, unpublished observations), which was similar to that reported in the dwarf rat (Gargosky et al 1995). Plasma GHBP levels in the saline-treated undernourished dams were similar to those measured in the saline-treated ad libitum fed rats.…”

Section: Discussionsupporting

confidence: 89%

“…Plasma GHBP levels in the saline-treated undernourished dams were similar to those measured in the saline-treated ad libitum fed rats. Similar serum GHBP levels were observed in pregnant dwarf rats with an isolated GH deficiency (Gargosky et al 1995). The effect on GHBP concentrations following GH and IGF-I treatment to pregnant rats has not been reported to date, but in male rats other studies have reported conflicting effects of hormone treatment on circulating GHBP levels.…”

Section: Discussionsupporting

confidence: 60%

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Administration of growth hormone or IGF-I to pregnant rats on a reduced diet throughout pregnancy does not prevent fetal intrauterine growth retardation and elevated blood pressure in adult offspring

Woodall¹,

Breier²,

Johnston³

et al. 1999

Journal of Endocrinology

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Increasing evidence from human epidemiological studies suggests that poor growth before birth is associated with postnatal growth retardation and the development of cardiovascular disease in adulthood. We have shown previously that nutritional deprivation in the pregnant rat leads to intrauterine growth retardation (IUGR), postnatal growth failure, changes in the endocrine parameters of the somatotrophic axis, and to increased blood pressure in later life. In the present study, we investigated whether administration of insulin-like growth factor-I (IGF-I) or bovine growth hormone (GH) during pregnancy could prevent IUGR and/or alter long-term outcome. Dams from day 1 of pregnancy throughout gestation received a diet of ad libitum available food or a restricted dietary intake of 30% of ad libitum fed dams. From day 10 of gestation, dams were treated for 10 days with three times daily subcutaneous injections of saline (100 µl), IGF-I (2 µg/g body weight) or GH (2 µg/g body weight). Maternal weight gain was significantly increased (P<0·001) in ad libitum fed dams treated with GH, (98·9 4·73 g) compared with the IGF-I (80·5 2·17 g) and saline-treated (70·7 2·65 g) groups. There was a small increase in maternal weight gain (P<0·06) in 30% ad libitum fed dams following GH (16·3 2·47 g) and IGF-I (15·8 1·97 g) treatment compared with saline (9·2 1·96 g). Whole spleen, kidney and carcass weights were significantly (P<0·05) increased in ad libitum fed and 30% ad libitum fed dams with GH treatment. Circulating IGF-I was significantly increased (P<0·001) in ad libitum fed dams with both IGF-I (369·6 32·33 ng/ml) and GH (457·9 33·32 ng/ml) compared with saline treatment (211·7 14·02 ng/ml), and with GH (223·4 23·72 ng/ml) compared with saline treatment (112·0 7·33 ng/ml) in 30% ad libitum fed dams. Circulating GH binding protein (GHBP) levels were significantly reduced (P<0·05) in GH-treated (299·1 51·54 ng/ml) compared with saline-treated (503·9 62·43 ng/ml) ad libitum fed dams, but were not altered in 30% ad libitum fed dams. There was no significant effect of either IGF-I or GH treatment on fetal weight, placental weight, fetal organ weights or circulating IGF-I levels in both ad libitum fed and 30% ad libitum fed fetuses. Offspring of 30% ad libitum fed dams remained significantly growth retarded postnatally and showed elevated blood pressure in later life. The increased maternal weight gain following IGF-I or GH administration, without an effect on fetal and placental weights, suggests a modification in the mode of maternal nutrient repartitioning during mid to late pregnancy at the expense of the fetus.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 60%

Administration of growth hormone or IGF-I to pregnant rats on a reduced diet throughout pregnancy does not prevent fetal intrauterine growth retardation and elevated blood pressure in adult offspring

Woodall¹,

Breier²,

Johnston³

et al. 1999

Journal of Endocrinology

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“…This may also be regulated by GH itself because continuous exposure to elevated GH in nonpregnant rats results in the up-regulation of GHBP (9,34). In contrast, however, it is interesting to note that a pregnancy-associated rise in GHBP is not driven by GH (35).…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of the Prolactin-binding Protein in Human Serum and Milk

Kline

Clevenger

2001

Journal of Biological Chemistry

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The actions of prolactin (PRL) are mediated by its receptor, a member of the superfamily of single transmembrane cytokine receptors. High affinity binding proteins for the closely related growth hormone have been found in the sera of several species including humans and are generated by alternative splicing or proteolysis of the growth hormone receptor extracellular domain (ECD). In contrast, no conclusive evidence has been presented that an analogous prolactin-binding protein (PRLBP) is expressed in human serum. Using both monoclonal and polyclonal antibodies generated against hPRL and the ECD of the human prolactin receptor, co-immunoprecipitation analyses of human serum identified a 32-kDa hPRLBP capable of binding both hPRL and human growth hormone. A measurable fraction of circulating PRL (36%) was associated with the hPRLBP. Despite well documented sex differences in serum hPRL levels, there were no significant differences in the levels of hPRLBP found in the sera of normal adult males and females (15.3 ؎ 1.3 ng/ml versus 13.4 ؎ 0.8 ng/ml, respectively (mean ؎ S.E.)). Immunoprecipitation studies also detected the PRLBP in human milk albeit at lower concentrations than found in sera. Deglycosylation did not alter its electrophoretic mobility, indicating an absence of carbohydrate moieties and suggesting that the hPRLBP spans most of the PRLR ECD, a result confirmed by limited proteolysis and mass spectrometry. The potential function of this serum chaperone was assessed in vitro by the addition of recombinant hPRLBP to the culture medium of the PRL-dependent Nb2 T-cell line. These studies revealed that the hPRLBP antagonizes PRL action, inhibiting PRL-driven growth in a dose-dependent manner.

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“…Although existing dwarf strains are useful in studies of GH or IGF-1 action (Skottner et al, 1989;Gargosky et al, 1995), neither show significant growth responses to GH secretagogues. Although existing dwarf strains are useful in studies of GH or IGF-1 action (Skottner et al, 1989;Gargosky et al, 1995), neither show significant growth responses to GH secretagogues.…”

Section: Discussionmentioning

confidence: 99%

Dominant dwarfism in transgenic rats by targeting human growth hormone (GH) expression to hypothalamic GH-releasing factor neurons.

Flavell¹,

Wells²,

Wells³

et al. 1996

The EMBO Journal

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Expression of human growth hormone (hGH) was targeted to growth hormone‐releasing (GRF) neurons in the hypothalamus of transgenic rats. This induced dominant dwarfism by local feedback inhibition of GRF. One line, bearing a single copy of a GRF‐hGH transgene, has been characterized in detail, and has been termed Tgr (for Transgenic growth‐retarded). hGH was detected by immunocytochemistry in the brain, restricted to the median eminence of the hypothalamus. Low levels were also detected in the anterior pituitary gland by radioimmunoassay. Transgene expression in these sites was confirmed by RT‐PCR. Tgr rats had reduced hypothalamic GRF and mRNA, in contrast to the increased GRF expression which accompanies GH deficiency in other dwarf rats. Endogenous GH mRNA, GH content, pituitary size and somatotroph cell number were also reduced significantly in Tgr rats. Pituitary adrenocorticotrophic hormone (ACTH) and thyroid‐stimulating hormone (TSH) levels were normal, but prolactin content, mRNA levels and lactotroph cell numbers were also slightly reduced, probably due to feedback inhibition of prolactin by the lactogenic properties of the hGH transgene. This is the first dominant dwarf rat strain to be reported and will provide a valuable model for evaluating the effects of transgene expression on endogenous GH secretion, as well as the use of GH secretagogues for the treatment of dwarfism.

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Upregulation of GH receptor and GH binding protein during pregnancy in the GH deficient rat

Cited by 6 publications

References 25 publications

Administration of growth hormone or IGF-I to pregnant rats on a reduced diet throughout pregnancy does not prevent fetal intrauterine growth retardation and elevated blood pressure in adult offspring

Administration of growth hormone or IGF-I to pregnant rats on a reduced diet throughout pregnancy does not prevent fetal intrauterine growth retardation and elevated blood pressure in adult offspring

Identification and Characterization of the Prolactin-binding Protein in Human Serum and Milk

Dominant dwarfism in transgenic rats by targeting human growth hormone (GH) expression to hypothalamic GH-releasing factor neurons.

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