scholarly journals Recombinant human growth hormone enhances tibial growth in peripubertal female rats but not in males

2000 ◽  
pp. 517-523 ◽  
Author(s):  
MA Rol De Lama ◽  
A Perez-Romero ◽  
JA Tresguerres ◽  
M Hermanussen ◽  
C Ariznavarreta

OBJECTIVE: A novel non-invasive technique termed microknemometry, which allows daily leg length measurement, was used to investigate the growth promoting effect of growth hormone (GH) on peripubertal rats. We compared the effect of different patterns of recombinant human (rh) GH administration to peripubertal male rats with the effect produced by two daily administrations of the same amount of rhGH to peripubertal female rats or adult male rats. Another group of peripubertal male rats was also submitted to a 3-day period of starvation, in order to study catch-up growth during refeeding and to determine whether this process could be stimulated by exogenous GH administration. RESULTS: GH treatment was unable to stimulate tibial growth or weight gain in peripubertal males, whereas a clear growth promoting effect was observed in female rats and also in adult male rats. Starvation caused a dramatic body weight loss, and a reduction in tibial growth rate. Peripubertal male rats gained body weight faster than unstarved animals during refeeding, although recovery was not complete after nine days. Tibial growth, however, was resumed at the same speed as in normally fed males. This means that no catch-up effect was observed after refeeding in animals either with or without GH treatment. CONCLUSIONS: During peripuberty, normal male rats grow at a maximal speed that cannot be further increased by exogenous GH treatment, whereas age-matched female rats or older males grow at a slower rate than peripubertal males. Thus, exogenous rhGH administration is capable of enhancing growth velocity.

1993 ◽  
Vol 294 (1) ◽  
pp. 159-165 ◽  
Author(s):  
P K Srivastava ◽  
D J Waxman

The sex-dependent expression and growth hormone (GH) regulation of rat liver glutathione S-transferase (GST) was examined using oligonucleotide probes that distinguish between closely related class Alpha (Ya1, Ya2, Yc) and class Mu (Yb1, Yb2, Yb3) GST mRNAs [Waxman, Sundseth, Srivastava and Lapenson (1992) Cancer Res. 52, 5797-5802]. Northern-blot analysis revealed that the steady-state levels of GST Ya1, Yb1 and Yb2 mRNAs are 2.5-3-fold higher in male as compared with female rat liver. In contrast, GST Yc and Ya2 mRNAs were expressed at a 2-3-fold higher level in female rat liver. Microsomal GST mRNA did not exhibit significant sex-dependent differences in rat liver. Treatment of male rats with GH by continuous infusion suppressed expression of the male-dominant GST Ya1, Yb1 and Yb2 mRNAs to levels at or below those found in female rat liver. This suppressive effect of GH was liver-specific, insofar as GH treatment did not alter kidney GST Ya1 mRNA levels. Hypophysectomy increased expression of the male-dominant GSTs, particularly in female rats (e.g. 8-fold elevation of GST Ya1 mRNA). GST Yc mRNA was increased approx. 2-fold in hypophysectomized males, indicating that this mRNA is subject to negative regulation by one or more pituitary-dependent factors. Continuous GH treatment of the hypophysectomized rats suppressed the expression of mRNA of GSTs Ya1, Yb1 and Yb2 when given as a continuous infusion, but not when given by an intermittent (twice daily) GH-injection schedule. Combination of continuous exposure to GH with thyroxine treatment resulted in a more complete suppression of GSTs Ya1, Yb1 and Yb2. In contrast, thyroxine increased the expression of GST Yc in hypophysectomized rats. These studies establish that several Alpha and Mu class GSTs are expressed in a sex-dependent fashion in adult rat liver, where they are regulated by multiple pituitary-dependent hormones through pretranslational mechanisms.


1957 ◽  
Vol 35 (1) ◽  
pp. 1113-1118
Author(s):  
George H. Beaton ◽  
Hannah Z. Banky ◽  
Audrey M. Haufschild

Doses of growth hormone which were minimal with respect to body weight increase were sufficient to produce significant alterations in liver alanine – glutamic transaminase and arginase activities and blood urea and amino nitrogen levels. The biochemical effects of the hormone appeared coincident with the body weight increase. Female rats showed a more pronounced response to growth hormone than did male rats. This sex difference was evident with respect to all of the metabolic alterations observed. Although it is not possible to state whether the metabolic alterations are direct effects of the hormone, they do take an integral part in bringing about the over-all biological effect.


1991 ◽  
Vol 124 (3) ◽  
pp. 283-289 ◽  
Author(s):  
Nisar A. Pampori ◽  
Arun K. Agrawal ◽  
Bernard H. Shapiro

Abstract. Hypophysectomy resulted in a total elimination of measurable circulating growth hormone with an associated loss of body weight gain. The typical sexually dimorphic plasma growth hormone patterns: pulsatile profiles in male rats and tonic-like secretion in female rats, were lost. The male- and female-dependent profiles of plasma growth hormone, monitored from serial blood collections, were restored by administering the hormone through a single electrically controlled external pump attached to an indwelling catheter, and by implanting osmotic pumps intraperitoneally, respectively. Restoring the natural patterns of plasma growth hormone in animals devoid of pituitaries, re-initiated body growth. However, the body weight gains in both sexes of hypophysectomized rats were much greater when rat growth hormone was introduced to the animals in a masculine (pulsatile) pattern that appeared to be independent of pulse frequency, rather than in a continuous feminine profile. Subcutaneous injections, the most commonly reported method of administration, produced low-amplitude, long-lasting plasma peaks that were not as effective as pulse infusion in restoring growth. The procedure allows manipulation of the hormone profile (i.e. number of pulses/day, pulse amplitude, and through duration in the pulsatile pattern, and plasma concentration in the tonic pattern) in order to identify, and thus study the presumed salient components of the pattern regulating growth hormone responses.


1964 ◽  
Vol 206 (5) ◽  
pp. 1137-1144 ◽  
Author(s):  
Robert L. Hazelwood ◽  
Barbara S. Hazelwood

Homogenates of adenohypophysial tissue obtained from alloxan-injected adult male rats varying in duration and severity of diabetes, as well as from diabetic rats maintained on an insulin-replacement regimen, were assayed in immature hypophysectomized female rats. The ability of these crude hypophysial extracts to encourage tibial cartilage width expansion, gain in body weight, and to depress hematocrit and blood urea levels was determined. Significant decrements in ability to increase epiphysial cartilage width and ability to depress hematocrits were noted 14 to 28 days following injection of alloxan. Increasing the intensity of the diabetic state was associated with decreased growth-promoting potency of hypophysial preparations as well as with decreased ability to influence hematological indices. Hypophysial extracts taken from insulin-treated diabetic rats contained more growth hormone than equivalent amounts of tissue obtained from control rats. It is concluded that the adenohypophyses of diabetic rats contain diminished amounts of growth hormone and that insulin repairs or encourages greater than normal accumulation of somatotrophin in these animals.


2020 ◽  
Author(s):  
Christopher D. Walker ◽  
Hannah G. Sexton ◽  
Mary-Louise Risher

ABSTRACTIntroductionPeer interactions are a crucial part of social and personal development, particularly during adolescence. Adolescence is characterized as a transitional developmental period between childhood and adulthood that is often associated with increased freedom, self-exploration, and novel experiences that are frequently peer-influenced. Due to newfound independence, there is a higher prevalence of alcohol consumption, which is in part due to the heightened social facilitating and rewarding effects of alcohol. Previous work shows that males and females who consume excessive alcohol during adolescence are at an increased risk of developing an alcohol use disorder (AUD) later in life. However, the contributions of social interaction and sexual dimorphism in alcohol consumption, two driving factors that influence AUD risk, are not fully understood. Many current rat models used to study the characteristics of alcohol use and the emergence of AUD coerce the animals into consuming liquid ethanol by the addition of a sweetener, which has been proven to confound results in adolescent rats. Here we use a novel self-administration ethanol vapor system to investigate the sexual dimorphic nature of socially facilitated ethanol consumption without the addition of sweeteners.MethodsAdolescent and adult male and female Sprague-Dawley rats underwent a novel voluntary chronic intermittent self-administration ethanol vapor paradigm. Nose poke-initiated self-administration vapor chambers (La Jolla Alcohol Research, Inc.) administered 20mg/L of vaporized ethanol or air (control) into the chamber in response to each individual nose poke. Beginning on postnatal day (PND) 30 or PND70, animals were placed in vapor chambers for 4 hours every other day for a total of 40 sessions. All animals underwent 10 sessions with their cagemate (social access) followed by 10 sessions in isolation (isolated access), a 10 day forced abstinence period, 10 sessions in isolation (isolated access), and 10 sessions with their cagemate (social access).ResultsFemale rats consumed more alcohol per body weight than age-matched males, while male rats increased ethanol preference over sessions regardless of age. In addition, all rats regardless of sex or age consumed more ethanol per body weight during the first social access session than during the subsequent isolated access sessions. Interestingly, there was an increase in ethanol consumption in adult male and females during the second social access session compared to the previous isolated access session that was not observed in either adolescent groups.ConclusionThese data demonstrate that female and male rats, regardless of age, are vulnerable to socially facilitated ethanol consumption. This is consistent with human data showing that increased levels of alcohol consumption among adolescents and young adults is associated with high levels of alcohol use within their social group (Sudhinaraset, Wigglesworth, & Takeuchi, 2016). However, only male rats demonstrate escalation across sessions. This may indicate that male rats are more vulnerable to escalated drinking and the emergence of ethanol dependence compared to females regardless of peer interaction. These data demonstrate that the self-administration ethanol vapor system is an effective alternative to other methods of voluntary ethanol administration for investigating factors that contribute to alcohol use and escalation.


2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Daniel J. Olivieri ◽  
Lauren J. Massingham ◽  
Jennifer L. Schwab ◽  
Jose Bernardo Quintos

Background. Growth hormone (GH) treatment increases the adult height of short children born small for gestational age (SGA). Catch-up growth is associated with a younger age, shorter height, and prepubertal status at the onset of GH treatment. We report a 12 11/12-year-old girl born SGA who received GH for 5 years without catch-up growth and was diagnosed with Noonan Syndrome (NS). Results. A 5-year-and-9-month-old 46, XX girl born SGA was started on GH treatment at a dose of 0.32 mg/kg/week. Her midparental target height is 158.6 cm. Endocrine work up showed an IGF-1 level 69 ng/ml (Normal (N): 55–238 ng/ml), IGFBP3 2.6 mg/L (N: 1.9–5.2 mg/L), TSH 3.2 mIU/L (N: 0.35–5.5 mIU/L), and a normal skeletal survey. Height was 96 cm (0.1%; Ht SDS −2.9), weight 14 kgs (1%; Wt SDS −2.3), and Tanner 1 breast and pubic hair were observed. Due to the poor catch-up growth on GH treatment, she was referred to Genetics to elucidate genetic or syndromic causes of short stature. She was noted to have posteriorly rotated ears and slight down slanting of the palpebral fissures. Genetic findings showed a heterozygous pathogenic variant in PTPN11 (c.922A > G (p.Asn308Asp)) diagnostic for NS. This finding is de novo given negative parental testing. She was noted to have a heterozygous missense variant of unknown significance (VUS) in FGFR3: c.746C > A (p.Ser249Tyr). FGFR3 is associated with multiple skeletal dysplasias including thanatophoric dysplasia, achondroplasia, and Crouzon syndrome and hypochondroplasia. Clinical correlation is poor for these syndromes. Conclusion. Diminished catch-up growth and response to GH treatment in a child born SGA led to the diagnosis of NS. The concomitant diagnosis of SGA and NS may have affected the responsiveness of this child to the growth promoting effect of GH treatment.


1957 ◽  
Vol 35 (12) ◽  
pp. 1113-1118 ◽  
Author(s):  
George H. Beaton ◽  
Hannah Z. Banky ◽  
Audrey M. Haufschild

Doses of growth hormone which were minimal with respect to body weight increase were sufficient to produce significant alterations in liver alanine – glutamic transaminase and arginase activities and blood urea and amino nitrogen levels. The biochemical effects of the hormone appeared coincident with the body weight increase. Female rats showed a more pronounced response to growth hormone than did male rats. This sex difference was evident with respect to all of the metabolic alterations observed. Although it is not possible to state whether the metabolic alterations are direct effects of the hormone, they do take an integral part in bringing about the over-all biological effect.


1969 ◽  
Vol 43 (1) ◽  
pp. 113-118 ◽  
Author(s):  
T. NIKKARI ◽  
M. VALAVAARA

SUMMARY The secretion rate of sebum in rats aged 3–14 weeks was determined by measuring the amount of acetone-extractable skin surface lipids produced during 2 days. The results were expressed as mg. sebum/100 g. body weight/2 days. The secretion rate of male rats was found to increase with age (from 16 mg./100 g. at 3 weeks to 35 mg./100 g. at 14 weeks), while that of female rats (16 mg./100 g.) remained unchanged. Hypophysectomy of 3-week-old female rats resulted in lowering of the secretion rate to 13 mg./100 g. at 10 weeks. No change in the secretion rate of the hypophysectomized animals occurred during either growth hormone or oestradiol treatment, but testosterone in doses of 1 mg. and 0·2 mg./day increased sebum production (to 37 mg./100 g. and 24 mg./100 g., respectively). The increase obtained with testosterone (0·2 mg./day) was smaller (20 mg./100 g.), when oestradiol (3 μg./day) was given simultaneously.


2003 ◽  
Vol 285 (2) ◽  
pp. H499-H506 ◽  
Author(s):  
Stéphanie Héon ◽  
Martin Bernier ◽  
Nicolas Servant ◽  
Stevan Dostanic ◽  
Chunlei Wang ◽  
...  

Doxorubicin (DOX), an anticancer drug, causes a dose-dependent cardiotoxicity. Some evidence suggests that female children have an increased risk for DOX-mediated cardiac damage. To determine whether the iron chelator dexrazoxane (DXR) could reduce DOX-induced cardiotoxicity in the young, we injected day 10 neonate female and male rat pups with a single dose of saline or DOX, DXR, or DXR + DOX (20:1). We followed body weight gain with growth, measured cardiac hypertrophy after a 2-wk swim exercise program, markers of apoptosis (Bcl-2, BAX, BNIP1, caspase 3 activation), oxidative stress (heme oxygenase 1, protein carbonyl levels), the chaperone protein clusterin, and the transcriptional activator early growth response gene-1 (Egr-1) in hearts of nonexercised and exercised rats on neonate day 38. All DOX-alone and DXR + DOX-treated rats showed decreased weight gain, with female rats affected earlier than male rats. DXR-alone, DOX-alone, and DXR + DOX-treated rats had an increased heart weight-to-body weight (heart wt/body wt) ratio after the exercise program with female rats showing the largest increase in heart wt/body wt. Drug-treated females also showed increased cardiac apoptosis, as measured by the increased expression of the proapoptotic proteins BAX and BNIP1 and the appearance of caspase 3 activation products, and oxidative stress, as measured by increased heme oxygenase 1 expression, and reduced Egr-1 and clusterin expression when compared with the similarly treated male rats. We conclude that DXR preinjection did not reduce DOX-induced noncardiac and cardiac damage and that young female rats were more susceptible to DXR and DOX toxicities than age-matched male rats.


2001 ◽  
Vol 91 (5) ◽  
pp. 2005-2009 ◽  
Author(s):  
Christian K. Roberts ◽  
Nosratola D. Vaziri ◽  
R. James Barnard

Dietary and humoral factors are thought to be involved in the development of hypertension. This study investigated the interaction between diet and gonadal hormone status in the development and reversibility of hypertension. Normal male and female and ovariectomized (OVX) female Fischer rats were placed on either a high-fat (primarily saturated), refined carbohydrate (sucrose) (HFS) or a low-fat, complex carbohydrate (LFCC) diet at 2 mo of age, and body weight and systolic blood pressure (BP) were measured. Male and OVX female rats were initially on the diets for 7 mo, whereas normal female rats were on the diets for 2 yr. After this initial phase, a group of rats from each of the normal HFS groups were converted to the LFCC diet for a period of 1 mo (males) and 2 mo (females). The OVX females were subcutaneously implanted with a 0.5-mg estradiol (E2) pellet for 1 mo. A significant rise in arterial BP occurred within 12 mo in female and only 2 mo in male rats on the HFS diet, exceeding 140 mmHg after 24 and 7 mo, respectively. Conversion from the HFS to the LFCC diet led to a normalization of BP in both female and male rats. HFS diet-induced hypertension was accelerated by OVX in female rats, approaching the pattern seen in male rats. The effect of OVX was completely reversed by E2replacement. BP did not significantly change in any of the LFCC groups at any time point, and E2 replacement had no effect on BP in the OVX LFCC group. All HFS groups had significantly greater body weight, with differences occurring sooner in the male and OVX rats compared with the female rats. Diet modification resulted in a partial but significant reduction of body weight, but E2replacement did not. These results demonstrate that long-term consumption of HFS diet induces hypertension in both genders and is reversible by diet modification. Hypertension is significantly delayed in females with functional ovaries. This protection is lost by OVX and restored by estrogen replacement. Thus hormone status contributes to the delayed onset of diet-induced hypertension in females compared with males.


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