Synergism of testosterone propionate with growth hormone in promoting growth of hypophysectomized rats: effect of sexual differentiation

1990 ◽  
Vol 127 (2) ◽  
pp. 249-256 ◽  
Author(s):  
J. Klindt ◽  
J. J. Ford ◽  
G. J. Macdonald
Keyword(s):  
Sexual Differentiation ◽  
Testosterone Propionate ◽  
Initial Study ◽  
Male Rats ◽  
Growth Enhancement ◽  
Growth Responses ◽  
Liver And Kidney ◽  
Hypophysectomized Rats ◽  
Synergistic Response ◽  
Rates Of Growth

ABSTRACT The effect of testosterone propionate (TP), alone and in combination with porcine GH, on the growth of hypophysectomized rats was investigated. An initial study determined doses of TP and GH which would result in a synergistic response. Hypophysectomized male rats, approximately 40 days of age, received GH at doses of 5, 25 and 62·5 μg/day administered in two injections/day at 08.00 and 16.00 h. At all doses of GH, administration of TP at 100 μg/day significantly enhanced the GH-stimulated rate of growth. This growth enhancement by TP was greatest in combination with GH at 25 μg/day. In a subsequent study, growth responses to 25 μg GH/day and 100 μg TP/day were examined in animals with differing degrees of sexual differentiation. Sex groups were: intact males, males castrated at 11 days of age and females administered 100 μg TP at 3 days of age (masculinized rats), and males castrated at 2 days of age and normal females (non-masculinized rats). In all sex groups, growth of hypophysectomized rats was stimulated by GH. Genetic sex and masculinization did not influence the response to GH. Masculinized hypophysectomized rats exhibited significantly greater rates of growth and final live, empty body, liver and kidney weights than non-masculinized hypophysectomized rats. All sex groups other than normal females responded synergistically to the combination treatment of GH plus TP. Rats that experienced neonatal exposure to testosterone became programmed to respond to testosterone and demonstrated greater rates of growth and body and organ weights when administered the combination of GH plus TP. These data indicate that TP synergizes with GH to promote growth of hypophysectomized rats appropriately programmed to respond. The ability to manifest a synergistic response is a differentiated trait dependent upon exposure to testosterone during the appropriate period of development. The time of differentiation of this ability to respond to testosterone occurs earlier than that for differentiation of body growth. Journal of Endocrinology (1990) 127, 249–256

scholarly journals Altered sexual differentiation of hepatic uridine diphosphate glucuronyltransferase by neonatal hormone treatment in rats

1979 ◽  
Vol 180 (2) ◽  
pp. 313-318 ◽  
Author(s):  
Coral A. Lamartiniere ◽  
Cindy S. Dieringer ◽  
Etsuko Kita ◽  
George W. Lucier
Keyword(s):  
Enzyme Activity ◽  
Adult Male ◽  
Sexual Differentiation ◽  
Reproductive Tract ◽  
Testosterone Propionate ◽  
Hormone Treatment ◽  
Male Rats ◽  
Ventral Prostate ◽  
Uridine Diphosphate ◽  
Neonatal Administration

The hepatic microsomal enzyme UDP-glucuronyltransferase undergoes a complex developmental pattern in which enzyme activity is first detectable on the 18th day of gestation in rats. Prepubertal activities are similar for males and females. However, postpubertal sexual differentiation of enzyme activity occurs in which male activities are twice those of females. Neonatal administration of testosterone propionate or diethylstilboestrol to intact animals resulted in lowered UDP-glucuronyltransferase activity in liver microsomal fractions of adult male rats, whereas no changes were observed in the adult females and prepubertal male and female animals. Neonatal administration of testosterone propionate and diethylstilboestrol adversely affected male reproductive-tract development as evidenced by decreased weights of testes, seminal vesicles and ventral prostate. Diethylstilboestrol also markedly decreased spermatogenesis. Hypophysectomy of adult male rats resulted in negative modulation of microsomal UDP-glucuronyltransferase and prevented the sexual differentiation of enzyme activity. In contrast hypophysectomy had no effect on female UDP-glucuronyltransferase activity. A pituitary transplant under the kidney capsule was not capable of reversing the enzyme effects of hypophysectomy, therefore suggesting that the male pituitary factor(s) responsible for positive modulation of UDP-glucuronyltransferase might be under hypothalamic control in the form of a releasing factor. Neonatal testosterone propionate and diethylstilboestrol administration apparently interfered with the normal sequence of postpubertal UDP-glucuronyltransferase sexual differentiation.

scholarly journals Different mechanisms of regulation of nuclear reduced nicotinamide–adenine dinucleotide phosphate-dependent 3-oxo steroid 5α-reductase activity in rat liver, kidney and prostate

1974 ◽  
Vol 142 (2) ◽  
pp. 273-277 ◽  
Author(s):  
Jan-Åke Gustafsson ◽  
Åke Pousette
Keyword(s):  
Testosterone Propionate ◽  
Reductase Activity ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Female Rats ◽  
Male Rats ◽  
Regulatory Mechanisms ◽  
Oestradiol Benzoate ◽  
Liver And Kidney ◽  
Reduced Nicotinamide Adenine Dinucleotide ◽  
Hydroxy Steroid

The regulatory mechanisms involved in the control of the nuclear NADPH-dependent 3-ketosteroid 5α-reductase (5α-reductase) activity were studied in liver, kidney and prostate. The substrate used was [1,2-3H]androst-4-ene-3,17-dione (androstenedione) (for liver and kidney) or [4-14C]androstenedione (for prostate). The hepatic nuclear 5α-reductase activity was greater in female than in male rats, was greater in adult than in prepubertal female rats, increased after castration of male rats, but was not affected by treatment with testosterone propionate or oestradiol benzoate. These regulatory characteristics are in part different from those previously described for the hepatic microsomal 5α-reductase. The renal nuclear metabolism of androstenedione, i.e. 5α reduction and 17β-hydroxy steroid reduction, was relatively unaffected by sex, age, castration and treatment with testosterone propionate. However, treatment of castrated male rats with oestradiol benzoate led to a significant increase in the 5α-reductase activity and a significant decrease in the 17β-hydroxy steroid reductase activity. Finally, the nuclear 5α-reductase activity in prostate was androgen-dependent, decreasing after castration and increasing after treatment with testosterone propionate. In conclusion, the nuclear 5α-reductase activities in liver, kidney and prostate seem to be under the control of distinctly different regulatory mechanisms. The hypothesis is presented that whereas the prostatic nuclear 5α-reductase participates in the formation of a physiologically active androgen, 5α-dihydrotestosterone, this may not be the true function of the nuclear 5α-reductase in liver and kidney. These enzymes might rather serve to protect the androgen target sites in the chromatin from active androgens (e.g. testosterone) by transforming them into less active androgens (e.g. 5α-androstane-3,17-dione and/or 5α-dihydrotestosterone).

scholarly journals The hypothalamic–hypophyseal–gonadal regulation of hepatic glutathione S-transferases in the rat

1981 ◽  
Vol 198 (1) ◽  
pp. 211-217 ◽  
Author(s):  
Coral A. Lamartiniere
Keyword(s):  
Adult Male ◽  
Sexual Differentiation ◽  
Male Rats ◽  
Adult Males ◽  
Glutathione S Transferase ◽  
Glutathione Conjugation ◽  
Inhibiting Factor ◽  
Hepatic Glutathione ◽  
Hypophysectomized Rats ◽  
Glutathione S Transferases

Hepatic glutathione S-transferase activities were determined with the substrates 1,2-dichloro-4-nitrobenzene and 1-chloro-2,4-dinitrobenzene. Sexual differentiation of glutathione S-transferase activities is not evident during the prepubertal period, but glutathione conjugation with 1,2-dichloro-4-nitrobenzene is 2–3-fold greater in adult males than in females. Glutathione conjugation with 1-chloro-2,4-dinitrobenzene is slightly higher in adult males than adult females. No change in activity was observed after postpubertal gonadectomy of males or females. Neonatal castration of males results in a significant decrease in glutathione conjugation with 1,2-dichloro-4-nitrobenzene. Hypophysectomy, or hypophysectomy followed by gonadectomy did result in significantly higher glutathione S-transferase activities in both sexes. These increases can be reversed by implanting an adult male or female pituitary or four prepubertal pituitaries under the kidney capsule. Postpubertal sexual differentiation of glutathione S-transferase activities is neither dependent on pituitary sexual differentiation nor pituitary maturation. Prolactin concentrations are inversely related to glutathione S-transferase activities in hypophysectomized rats with or without ectopic pituitaries. Somatotropin exogenously administered to hypophysectomized rats results in decreased glutathione S-transferase activities, whereas prolactin has no effect. Adult male rats treated neonatally with monosodium l-glutamate to induce arcuate nucleus lesions of the hypothalamus have decreased glutathione S-transferase activities towards 1,2-dichloro-4-nitrobenzene and decreased somatotropin concentrations. Our experiments suggests that sexual differentiation of hepatic glutathione S-transferase is a result of a hypothalamic inhibiting factor in the male (absent in the female). This postpubertally expressed inhibiting factor acts on the pituitary to prevent secretion of a pituitary inhibiting factor (autonomously secreted by the female), resulting in higher glutathione S-transferase activities in the adult male than the adult female.

EFFECTS OF DIHYDROTESTOSTERONE AND OESTRADIOL ON SEXUAL DIFFERENTIATION IN MALE RATS

1980 ◽  
Vol 84 (3) ◽  
pp. 397-407 ◽  
Author(s):  
P. VAN DER SCHOOT
Keyword(s):  
Sexual Differentiation ◽  
Testosterone Propionate ◽  
Neonatal Period ◽  
Combined Treatment ◽  
Female Rats ◽  
Male Rats ◽  
Normal Male ◽  
Oestradiol Benzoate ◽  
The Brain ◽  
Copulatory Behaviour

Adult male rats which had been castrated at birth and treated with the non-aromatizable androgen dihydrotestosterone propionate (DHTP) showed incomplete copulatory behaviour. When tested with oestrous female rats during treatment with testosterone propionate (TP) they readily mounted these females and showed frequent penile intromissions but rarely ejaculated. In a long series of observations the proportion of ejaculating rats in tests of 30 min did not exceed 50%. Neonatally castrated rats treated with DHTP during infancy thus seemed to be capable of ejaculation in adulthood during treatment with TP, but the threshold for the occurrence of the ejaculatory reflex seemed to be higher than in normal male rats. By replacing treatment in adulthood with TP by a combined treatment with DHTP and oestradiol benzoate (OB), the frequency of ejaculation was not increased. It was concluded that the incomplete copulatory behaviour was not due to reduced efficiency of aromatization of androgen within the brain of these rats. The addition of OB to DHTP during the neonatal period of treatment enhanced the frequency of ejaculation in adulthood. The combined treatment of 0·1 mg DHTP on days 1, 3 and 5 with 0·01 mg OB on day 1 made adult copulatory behaviour during treatment with TP indistinguishable from that of rats castrated on day 10 or rats castrated at birth and treated with TP during infancy. It was concluded that the masculine organization of systems and structures involved in the display of male copulatory behaviour occurs under the influence of both non-aromatizable androgen and oestrogen, oestrogen being most likely the substance required to 'organize' the central nervous aspects of the regulation of this behaviour. The absence neonatally of nonaromatizable androgen and/or oestrogen results in specific deficiencies in adult copulatory behaviour as compared with the behaviour of normal male rats.

PEPTIDASE ACTIVITY IN THE HYPOTHALAMI OF RATS TREATED NEONATALLY WITH OESTROGEN

1973 ◽  
Vol 72 (1) ◽  
pp. 9-17 ◽  
Author(s):  
E. C. Griffiths ◽  
K. C. Hooper
Keyword(s):  
Sexual Differentiation ◽  
Critical Period ◽  
Testosterone Propionate ◽  
Marked Decrease ◽  
Reproductive Function ◽  
Female Rats ◽  
Male Rats ◽  
Peptidase Activity ◽  
Rat Hypothalamus ◽  
Lh Secretion

ABSTRACT The previous paper (Griffiths & Hooper 1973) described the activity of certain hypothalamic peptidases following orchidectomy and testosterone propionate injection, and suggested that changes in enzyme levels may be used as an index of gonadotrophin release in male rats, in a similar way to that previously described for female rats (Griffiths & Hooper 1972a). Using this approach, the effect of neonatally administered oestrogen on the hypothalamus was investigated. The marked increase in supernatant activity in male rats and the equally marked decrease in supernatant activity in female rats, both injected during the critical period of hypothalamic sexual differentiation, are interpreted as indicating decreased LH secretion in males and increased LH secretion in females respectively. It can be concluded that the changes in reproductive function produced by neonatally administered oestrogen are caused by alterations in LH-RF metabolism and that the peptidases in the rat hypothalamus are responsible for this metabolism.

Growth responses of seven major co-occurring tree species of the northeastern United States to elevated CO2

1990 ◽  
Vol 20 (9) ◽  
pp. 1479-1484 ◽  
Author(s):  
F. A. Bazzaz ◽  
J. S. Coleman ◽  
S. R. Morse
Keyword(s):  
Tree Species ◽  
Sugar Maple ◽  
Growth Enhancement ◽  
Black Cherry ◽  
Red Maple ◽  
Growth Responses ◽  
White Pine ◽  
American Beech ◽  
Harvard Forest ◽  
Paper Birch

We examined how elevated CO2 affected the growth of seven co-occurring tree species: American beech (Fagusgrandifolia Ehrh.), paper birch (Betulapapyrifera Marsh.), black cherry (Prunusserotina Ehrh.), white pine (Pinusstrobus L.), red maple (Acerrubrum L.), sugar maple (Acersaccharum Marsh.), and eastern hemlock (Tsugacanadensis (L.) Carr). We also tested whether the degree of shade tolerance of species and the age of seedlings affected plant responses to enhanced CO2 levels. Seedlings that were at least 1 year old, for all species except beech, were removed while dormant from Harvard Forest, Petersham, Massachusetts. Seeds of red maple and paper birch were obtained from parent trees at Harvard Forest, and seeds of American beech were obtained from a population of beeches in Nova Scotia. Seedlings and transplants were grown in one of four plant growth chambers for 60 d (beech, paper birch, red maple, black cherry) or 100 d (white pine, hemlock, sugar maple) under CO2 levels of 400 or 700 μL•L−1. Plants were then harvested for biomass and growth determinations. The results showed that the biomass of beech, paper birch, black cherry, sugar maple, and hemlock significantly increased in elevated CO2, but the biomass of red maple and white pine only marginally increased in these conditions. Furthermore, there were large differences in the magnitude of growth enhancement by increased levels of CO2 between species, so it seems reasonable to predict that one consequence of rising levels of CO2 may be to increase the competitive ability of some species relative to others. Additionally, the three species exhibiting the largest increase in growth with increased CO2 concentrations were the shade-tolerant species (i.e., beech, sugar maple, and hemlock). Thus, elevated CO2 levels may enhance the growth of relatively shade-tolerant forest trees to a greater extent than growth of shade-intolerant trees, at least under the light and nutrient conditions of this experiment. We found no evidence to suggest that the age of tree seedlings greatly affected their response to elevated CO2 concentrations.

The protective role of luteolin against the methotrexate-induced hepato-renal toxicity via its antioxidative, anti-inflammatory, and anti-apoptotic effects in rats

2021 ◽  
pp. 096032712199190
Author(s):  
AA Dar ◽  
A Fehaid ◽  
S Alkhatani ◽  
S Alarifi ◽  
WS Alqahtani ◽  
...  
Keyword(s):  
Renal Toxicity ◽  
Histopathological Examination ◽  
Protective Role ◽  
Male Rats ◽  
Antioxidant Enzyme Activities ◽  
Serum Samples ◽  
Liver And Kidney ◽  
Anti Inflammatory ◽  
Induced Changes ◽  
Apoptotic Effects

Methotrexate (MTX) is frequently used drug in treatment of cancer and autoimmune diseases. Unfortunately, MTX has many side effects including the hepato-renal toxicity. In this study, we hypothesized that Luteolin (Lut) exhibits protective effect against the MTX-induced hepato-renal toxicity. In order to investigate our hypothesis, the experiment was designed to examine the effect of exposure of male rats to MTX (20 mg/kg, i.p., at day 9) alone or together with Lut (50 mg/kg, oral for 14 days) compared to the control rats (received saline). The findings demonstrated that MTX treatment induced significant increases in the liver and kidney functions markers in serum samples including Aspartate transaminase (AST), Alanine transaminase (ALT), creatinine, urea and uric acid. MTX also mediated an oxidative stress expressed by elevated malondialdehyde (MDA) level and decreased level of reduced glutathione (GSH), antioxidant enzyme activities, and downregulation of the Nrf2 gene expression as an antioxidant trigger. Moreover, the inflammatory markers (NF-κB, TNF-α, and IL-1β) were significantly elevated upon MTX treatment. In addition, MTX showed an apoptotic response mediated by elevating the pro-apoptotic (Bax) and lowering the anti-apoptotic (Bcl-2) proteins. All of these changes were confirmed by the observed alterations in the histopathological examination of the hepatic and renal tissues. Lut exposure significantly reversed all the MTX-induced changes in the measured parameters suggesting its potential protective role against the MTX-induced toxicity. Finally, our findings concluded the antioxidative, anti-inflammatory and anti-apoptotic effects of Lut as a mechanism of its protective role against the MTX-induced hepato-renal toxicity in rats.

The Obesogenic Potency of Various High-Caloric Diet Compositions in Male Rats, and Their Effects on Expression of Liver and Kidney Proteins Involved in Drug Elimination

2017 ◽  
Vol 106 (6) ◽  
pp. 1650-1658 ◽  
Author(s):  
Ali Abdussalam ◽  
Osama H. Elshenawy ◽  
Yousef A. bin Jardan ◽  
Ayman O.S. El-Kadi ◽  
Dion R. Brocks
Keyword(s):  
Male Rats ◽  
Drug Elimination ◽  
Liver And Kidney ◽  
High Caloric Diet

scholarly journals Evaluation of the Coating with TiO2 Nanoparticles as an Option for the Improvement of the Characteristics of NiTi Archwires: Histopathological, Cytotoxic, and Genotoxic Evidence

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Javier Morán-Martínez ◽  
Roberto Beltrán del Río-Parra ◽  
Nadia Denys Betancourt-Martínez ◽  
Rubén García-Garza ◽  
Joel Jiménez-Villarreal ◽  
...  
Keyword(s):  
Cell Viability ◽  
Blood Sample ◽  
Tio2 Nanoparticles ◽  
Niti Alloy ◽  
Renal Tissue ◽  
Male Rats ◽  
Histopathological Analysis ◽  
Liver And Kidney ◽  
The Times ◽  
Nuclear Alterations

For the EPD, different voltages and different times were used. Male rats were used in four groups (n=3) with different treatments. The blood sample was obtained for genotoxic analysis and liver and kidney organs were removed for histopathological analysis. The amount of NPs TiO2 deposited on the samples of the arches increases gradually in the times of 15 and 30 s. At all voltages, however, at 45, 60, 75, and 90 s, there is an increase up to 25 V. Cell viability in lymphocytes treated with TiO2 NPs did not cause genotoxicity. In the histopathological findings of hepatic and renal tissue, nuclear alterations and necrosis were observed. The objective of the study was to improve the physical and biocompatibility characteristics of the NiTi arches for which the EPD is used. The technique for the deposition of TiO2 NPs was used, where this technique could be used as an economical and versatile way to perform homogeneous depositions even on surfaces with the complexity of the NiTi alloy. As for genotoxicity and cytotoxicity, we continue to have controversial results.

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