Effect of exogenous growth hormone on somatic growth, gonadal development, and hepatic CYP2C11 and CYP2C12 expression in prepubertal intact male rats

2001 ◽  
Vol 79 (4) ◽  
pp. 352-361
Author(s):  
Masahiko Kawai ◽  
Stelvio M Bandiera ◽  
Thomas KH Chang ◽  
Gail D Bellward
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Cytochrome P450 ◽  
Somatic Growth ◽  
Skeletal Growth ◽  
Male Rats ◽  
Intact Male ◽  
Hepatic Expression ◽  
Testicular Weight ◽  
Exogenous Growth

The influence of exogenous growth hormone (GH) on pubertal maturation, as assessed by growth, age of preputial separation, testicular development, and hepatic expression of sexually dimorphic cytochrome P450 (CYP) enzymes, was investigated. Treatment of 22-day old prepubertal intact male rats with twice daily subcutaneous (sc) injections of rat recombinant GH (0.12 µg/g body weight) for 12 or 21 days did not affect body weight, skeletal growth, or testicular weight. By comparison, GH suppressed hepatic CYP2C11 enzyme activity, protein, and mRNA levels but induced CYP2C12 expression. GH suppressed CYP2C11 expression by approximately 60% in prepubertal rats as compared with 30% in adult rats, whereas it increased CYP2C12 levels to 80% of the normal female levels but had no effect in adult male rats. Twice daily intravenous injections of GH suppressed CYP2C11 only. Increasing the sc dose of GH 30-fold produced little or no additional change in CYP2C11 or CYP2C12 expression, whereas it modestly increased body weight and skeletal growth and reduced testicular weight. Overall, the present study provides the first demonstration that prepubertal administration (22-33 days of age) of GH at a pharmacologically relevant dose (0.12 µg/g twice daily) suppressed hepatic expression of CYP2C11 in 34-day-old intact male rats, suggesting that in this age group the liver is intrinsically responsive to transcription factors involved in the regulation of GH-dependent, sex-specific CYP gene expression. A higher dose (3.6 µg/g) of GH administered during the prepubertal period was required to elicit a modest effect on somatic growth and gonadal development.Key words: cytochrome P450, CYP2C11, CYP2C12, growth hormone, preputial separation, pubertal development, testosterone.

Involvement of physiological prolactin levels in growth and prolactin receptor content of prostate glands and testes in developing male rats

1992 ◽  
Vol 132 (3) ◽  
pp. 449-459 ◽  
Author(s):  
B. Pérez-Villamil ◽  
E. Bordiú ◽  
M. Puente-Cueva
Keyword(s):  
Body Weight ◽  
Male Rats ◽  
Ventral Prostate ◽  
Serum Prolactin ◽  
Plasma Prolactin ◽  
Stages Of Development ◽  
Continuous Increase ◽  
Testosterone Levels ◽  
Testicular Weight

ABSTRACT We have investigated the role of physiological prolactin levels in the development of prepubertal male rats. Prolactin GH and testosterone levels, as well as body, ventral prostate and testicular weight, have been analysed in both control and bromocriptine-treated rats between 21 and 60 days of life. Furthermore the role of prolactin in the regulation of its own receptors has also been studied during the same period. In control rats, prolactin levels showed a prepubertal peak of secretion at 25 days of age. At this time GH and testosterone levels were low and did not show any significant variation. After this age, prolactin levels increased more gradually; determinations of GH showed great variation with low levels in most of the rats and very high values in the other animals; testosterone levels remained low until day 35 after which they increased. Simultaneously with the serum prolactin peak on day 25, a decrease in prolactin-binding capacity of ventral prostate glands, was observed and a maximum rate of body, prostate and testicular weight gain was obtained. Furthermore, in rats with pharmacologically suppressed serum prolactin levels (lower than 1 μg/l), prolactin binding to prostate glands as well as the weight of body, ventral prostate and testes were lower than in control animals. When results were expressed in mg prostate or testes/g body weight, testes from 25-day-old treated rats weighed significantly less than controls. The later stages of development, from days 25 to 60, were characterized by an initial decline in serum prolactin levels at 29 days of age which was followed by a continuous increase until adult values were reached. During this period, prostatic prolactin receptors which were at their lowest value at 33 days of age showed a gradual rise parallel with the observed increase in plasma prolactin levels. When testicular tissue was analysed, no changes in prolactin-binding sites caused by sexual maturation were observed. The present results indicate that physiological prolactin secretion has a specific effect on the normal increase in the prostate, testes and body weight and clearly is also implicated in the regulation of its prostatic receptors at the earlier stages of development. Journal of Endocrinology (1992) 132, 449–459

EFFECTS OF TESTOSTERONE MEDIATED OR MODULATED BY PITUITARY FACTORS

1975 ◽  
Vol 67 (1) ◽  
pp. 71-79 ◽  
Author(s):  
P. DE MOOR ◽  
M. ADAM-HEYLEN ◽  
H. VAN BAELEN ◽  
G. VERHOEVEN
Keyword(s):  
Body Weight ◽  
Testosterone Propionate ◽  
Total Body Weight ◽  
Seminal Vesicles ◽  
Female Rats ◽  
Male Rats ◽  
Intact Male ◽  
Adult Rats ◽  
Organ Weights ◽  
Total Body

SUMMARY Adult rats of both sexes were either gonadectomized or hypophysectomized and gonadectomized. Three to eight weeks later they were treated for 14 consecutive days with oil or with 75 or 200 μg testosterone propionate (TP) per 100 g body weight. The animals were killed and for each sex the gonadectomized animals were compared with the hypophysectomized-gonadectomized animals as far as their NADPH- and NADH-dependent 3α-hydroxysteroid dehydrogenases (3α-HSD) in renal microsomes, transcortin levels in serum and five organ weights relative to total body weight were concerned. For two of the latter, i.e. the relative kidney and prostatic weights, no significant differences were found. Transcortin levels, relative adrenal weights and renal NADPH-dependent 3α-HSD activities were higher in oil-treated gonadectomized animals than in oil-treated hypophysectomized-gonadectomized animals. The opposite was found for the relative weights of uterus and seminal vesicles and renal NADH-dependent 3α-HSD activities. These differences between gonadectomized and hypophysectomized-gonadectomized animals disappeared after TP treatment as far as transcortin levels were concerned but remained for the five other parameters. After gonadectomy sexual differences subsisted for all parameters studied. But whereas intact male rats had higher NADH-dependent 3α-HSD activities than female rats the opposite was found after gonadectomy. After gonadectomy plus hypophysectomy the between sex differences disappeared as far as transcortin levels were concerned but remained in the other parameters studied.

The 2001 Veylien Henderson Award of the Society of Toxicology of Canada. Positive and negative transcriptional regulation of cytochromes P450 by polycyclic aromatic hydrocarbons

2003 ◽  
Vol 81 (1) ◽  
pp. 59-77 ◽  
Author(s):  
David S Riddick ◽  
Chunja Lee ◽  
Anahita Bhathena ◽  
Yoav E Timsit
Keyword(s):  
Growth Hormone ◽  
Transcriptional Regulation ◽  
Cytochrome P450 ◽  
Aromatic Hydrocarbon ◽  
Aromatic Hydrocarbons ◽  
Cytochromes P450 ◽  
Biological Significance ◽  
Male Rats ◽  
Cytochrome P450 1A1 ◽  
Aromatic Hydrocarbon Receptor

Most responses to aromatic hydrocarbons such as 3-methylcholanthrene (MC) and 2,3,7,8-tetrachlorodibenzo-p-dioxin are mediated by the aromatic hydrocarbon receptor (AHR). The AHR regulates induction of drug-metabolizing enzymes such as cytochrome P450 1A1. However, the expression of several genes of biological significance is decreased by these chemicals. We are examining the mechanisms by which aromatic hydrocarbons suppress constitutive hepatic cytochromes P450, especially the male-specific rat liver cytochrome P450 2C11 (CYP2C11), which is regulated by pulsatile growth hormone (GH) secretion. Aromatic hydrocarbons suppress CYP2C11 via a transcriptional mechanism both in vivo and in cultured hepatocytes, and the AHR appears to be involved; however, studies of protein–DNA interactions and reporter genes driven by the CYP2C11 5'-flanking region have not provided a definitive mechanism for this response. MC attenuates the ability of GH to stimulate hepatic CYP2C11 expression in hypophysectomized (hypx) male rats, and this prompted studies of effects of aromatic hydrocarbons on hepatic GH signaling pathways as a novel aspect of endocrine disruption. Our studies with hypx rats also suggest that the hepatic AHR protein is regulated by a pituitary factor(s). The goal of these molecular mechanistic studies is to improve our understanding of how environmental contaminants modulate the expression of genes coding for xenobiotic- and hormone-metabolizing enzymes.Key words: aromatic hydrocarbons, cytochrome P450, aromatic hydrocarbon receptor, growth hormone, transcriptional regulation.

THE COMPARATIVE ACTIONS OF TESTOSTERONE PROPIONATE AND 5α-ANDROSTAN17β-OL-3-ONE PROPIONATE ON THE REPRODUCTIVE BEHAVIOUR, PHYSIOLOGY AND MORPHOLOGY OF MALE RATS

1971 ◽  
Vol 51 (2) ◽  
pp. 241-NP ◽  
Author(s):  
H. H. FEDER
Keyword(s):  
Body Weight ◽  
Seminal Vesicle ◽  
Sexual Behaviour ◽  
Testosterone Propionate ◽  
Reproductive Behaviour ◽  
Male Rats ◽  
Male Sexual Behaviour ◽  
Testicular Weight ◽  
Seminal Vesicle Weight ◽  
Experienced Adult

SUMMARY 5α-Androstan-17β-ol-3-one in its free or in its propionate form was injected systemically (125 μg/day/rat) into sexually experienced, adult, castrated, male rats. These compounds were ineffective in activating masculine behaviour patterns, despite having measurable effects on body weight, seminal vesicle weight and penile morphology. The propionate form also had strong anti-gonadotrophic properties, since when it was injected for 6 days into intact, immature, male rats it significantly reduced testicular weight. In contrast, testosterone propionate (125 μg/day/rat) restored male sexual behaviour to the levels found before castration when injected systemically. Testosterone propionate also affected body weight, seminal vesicle weight, penile morphology and the testicular weight of immature males. These effects may have been due in part to conversion of testosterone to 5α-androstan-17β-ol-3-one, but this metabolic step does not seem to be obligatory for activation of male sexual behaviour in rats.

The effect of a single injection of estradiol benzoate on thyroid function in intact male rats

1968 ◽  
Vol 46 (4) ◽  
pp. 697-700 ◽  
Author(s):  
K. Brown-Grant
Keyword(s):  
Body Weight ◽  
Thyroid Gland ◽  
Thyroid Function ◽  
Dose Level ◽  
Adult Male ◽  
Single Injection ◽  
Estradiol Benzoate ◽  
Male Rats ◽  
Intact Male ◽  
Federation Proc

The changes observed in the metabolism of radioiodide and radiophosphorus by the thyroid gland of intact adult male rats following a single injection of estradiol benzoate (4 μg/100 g body weight) are consistent with the suggestion (F. Labrie, G. Pelletier, and C. Fortier. Federation Proc. 26, 484 (1967). Abstr.) that at this dose level estrogen causes a hypersecretion of TSH in such animals.

THE INTERRELATION OF THE GROWTH AND METABOLIC RESPONSES TO ANTERIOR PITUITARY GROWTH HORMONE ADMINISTRATION

1957 ◽  
Vol 35 (1) ◽  
pp. 1113-1118
Author(s):  
George H. Beaton ◽  
Hannah Z. Banky ◽  
Audrey M. Haufschild
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Amino Nitrogen ◽  
The Body ◽  
Female Rats ◽  
Male Rats ◽  
Weight Increase ◽  
Metabolic Alterations ◽  
Nitrogen Levels ◽  
Body Weight Increase

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.

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
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Adult Male ◽  
Female Rats ◽  
Male Rats ◽  
Invasive Technique ◽  
Promoting Effect ◽  
Gh Treatment ◽  
Catch Up ◽  
Growth Promoting

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.

STUDIES ON THE EFFECT OF HORMONE ADMINISTRATION ON BODY WEIGHT AND ON TIBIAL EPIPHYSIAL CARTILAGE WIDTH IN INTACT, HYPOPHYSECTOMIZED AND ADRENALECTOMIZED RATS

1963 ◽  
Vol 25 (4) ◽  
pp. 473-482 ◽  
Author(s):  
HELEN E. C. CARGILL THOMPSON ◽  
G. P. CREAN
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Young Male ◽  
Total Body Weight ◽  
Male Rats ◽  
Unilateral Nephrectomy ◽  
Hormone Administration ◽  
Epiphysial Cartilage ◽  
Hypophysectomized Rats ◽  
Total Body

SUMMARY 1. The effects of feeding, hormone administration, unilateral nephrectomy and adrenalectomy on width of tibial cartilage and total body weight in intact and hypophysectomized young male rats were measured. 2. Unilateral nephrectomy and adrenalectomy have no effect on the cartilage width of both intact and hypophysectomized rats, although adrenalectomy causes a loss in weight in the intact rat. 3. Intact rats, both young and adult, fed enough to maintain but not to put on weight, show a reduction of cartilage width to hypophysectomized levels. 4. Growth hormone alone (1 mg. and 3 mg./day for 14 days) causes a marked increase in cartilage width but only a 50–60% increase in total body weight in the hypophysectomized rat. 5. Adrenocorticotrophin (ACTH: 2 i.u./day for 14 days) causes a significant reduction in both cartilage width and total body weight in the hypophysectomized rat. 6. Thyrotrophin (TSH: 1 i.u./day) and Prolactin (1 mg. and 2 mg./day) caused significant increases in both total body weight and cartilage width in the hypophysectomized rat. 7. Luteinizing hormone (LH: 0·01 mg./day) together with follicle stimulating hormone (FSH: 1·0 mg./day) caused a significant increase in body weight, but had no effect on cartilage width in the hypophysectomized rat. 8. Both doses of combined hormones (growth hormone, ACTH, TSH, prolactin, FSH and LH administered together) caused a marked increase in cartilage width and a smaller increase in total body weight in the hypophysectomized rat.

scholarly journals Regulation of serum leptin levels by gonadal function in rats

1999 ◽  
pp. 468-473 ◽  
Author(s):  
L Pinilla ◽  
LM Seoane ◽  
L Gonzalez ◽  
E Carro ◽  
E Aguilar ◽  
...  
Keyword(s):  
Body Weight ◽  
Estrous Cycle ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Internal Diameter ◽  
External Diameter ◽  
Gonadal Function ◽  
Intact Male ◽  
Serum Leptin

The aim of this study was to investigate the regulation of serum leptin levels by gender and gonadal steroid milieu. Thus, we measured serum leptin levels by radioimmunoassay in (a) intact male and female rats, (b) female rats at different stages of the estrous cycle and (c) ovariectomized or orchidectomized rats. Gonadectomized groups were or were not implanted with silastic capsules (10 or 30 mm in length, 1.519mm internal diameter; 3.06 mm external diameter) containing estradiol or testosterone and decapitated two weeks later. We found (i) intact female rats weighing 50 g, 250 g and 300 g exhibited higher serum leptin concentrations than intact male rats of similar body weight; (ii) leptin concentrations were not affected by the phase of the estrous cycle; (iii) two weeks after gonadectomy serum leptin concentrations increased in both male (from 4.47+/-1.87 to 8.76+/-1.24 ng/ml) and female (from 1.97+/-0.46 to 5.29+/-0.51 ng/ml) rats. The ovariectomy-induced increase in serum leptin levels was not dependent, at least completely, on changes in body weight since it could be observed when comparisons were made between ovariectomized rats and intact rats in estrus matched for body weight. In contrast the effect of orchidectomy on serum leptin levels appears to be dependent on changes in body weight since it was no longer observed when comparisons were made with a group of intact male rats matched for body weight. In conclusion, these results suggest that serum leptin concentrations are controlled by gonadal function either directly or as a consequence of changes in body weight.

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