The in-vitro transformation of [3H]dehydroepiandrosterone into its principal metabolites in the adrenal cortex of adult castrated male rats and following steroid treatment

1989 ◽  
Vol 121 (3) ◽  
pp. 419-424 ◽  
Author(s):  
M. Canonaco ◽  
S. Andò ◽  
A. Valenti ◽  
R. Tavolaro ◽  
M. L. Panno ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Adult Male ◽  
Testosterone Propionate ◽  
Reductase Activity ◽  
Male Rats ◽  
Adrenal Androgen ◽  
Oestradiol Benzoate ◽  
Rat Adrenals ◽  
Low Testosterone

ABSTRACT The adrenal gland of castrated adult male rats metabolized [3H]dehydroepiandrosterone in vitro to Δ4-androsten-3,17-dione (4AD), testosterone, dihydrotestosterone (DHT) and 5α-androstane-3,17-dione (5αAD). Despite the low testosterone values, DHT and 5αAD were higher 30 and especially 60 days after castration, with raised 4AD:testosterone and decreased testosterone:DHT ratios. The 5α-reductase activity thus appears to increase with time after castration. Fourteen days after castration, 4AD was the only metabolite that was raised compared with intact animals, and testosterone was comparable in sham-operated and castrated rats. The administration of testosterone propionate to castrated rats restored testosterone values to those of intact rat adrenals, whereas 4AD values were greater. The administration of dihydrotestosterone propionate also yielded higher levels of 4AD, in the presence of a lower testosterone value. After administration of oestradiol benzoate, 4AD values were lower especially compared with the other hormone-treated groups, and there was an unexpectedly high testosterone value. These data indicate that the adrenal gland contributes to the production of androgens, as previously noted by Andò, Canonaco, Beraldi et al. (1988) who showed increased plasma 4AD and testosterone levels in adult male rats 30 days after castration. Furthermore, adrenal androgen production in castrated animals is differentially regulated by sex steroids. Journal of Endocrinology (1989) 121, 419–424

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).

TESTOSTERONE AND OESTRADIOL SUPPRESSION OF LH AND FSH IN ADULT MALE RATS: DURATION OF CASTRATION, DURATION OF TREATMENT AND COMBINED TREATMENT

1973 ◽  
Vol 73 (1) ◽  
pp. 11-21 ◽  
Author(s):  
R. S. Swerdloff ◽  
P. C. Walsh
Keyword(s):  
Adult Male ◽  
Testosterone Propionate ◽  
Combined Treatment ◽  
Male Rats ◽  
Low Doses ◽  
Duration Of Treatment ◽  
Serum Lh ◽  
Oestradiol Benzoate ◽  
Hypothalamic Pituitary Axis ◽  
Androgen Effect

ABSTRACT The effects of androgens and oestrogens on serum LH and FSH in castrated rats were evaluated with regard to the modifying influences of duration of castration, duration of treatment and combined oestrogen-androgen effect. Serum LH was not greatly influenced by these variables. In contrast, serum FSH was shown to be more resistant to suppression by both steroids after at least five days of castration, requiring a longer duration of treatment to be suppressed to intact levels. Combined treatment of submaximally suppressive doses of testosterone propionate and oestradiol benzoate resulted in no additive effect on lowering serum FSH. Low doses of both androgens and oestrogens resulted in elevated levels of serum LH and FSH, suggesting that the adult male hypothalamic-pituitary axis may be responsive to positive feedback. In all studies, testosterone preferentially suppressed serum LH as compared to serum FSH. In contrast, oestradiol administration produced parallel inhibition of both LH and FSH. It is emphasized that neither oestrogen nor androgen alone, nor in combination, resulted in preferential inhibition of serum FSH over LH.

EFFECTS OF TESTOSTERONE PROPIONATE, 5α-DIHYDROTESTOSTERONE PROPIONATE AND OESTRADIOL BENZOATE ON SERUM LEVELS OF LH AND FSH IN THE CASTRATED ADULT MALE RAT

1974 ◽  
Vol 77 (4) ◽  
pp. 643-654 ◽  
Author(s):  
H. L. Verjans ◽  
K. B. Eik-Nes ◽  
J. H. Aafjes ◽  
F. J. M. Vels ◽  
H. J. van der Molen
Keyword(s):  
Adult Male ◽  
Testosterone Propionate ◽  
Serum Levels ◽  
Seminal Vesicles ◽  
Male Rats ◽  
Male Rat ◽  
Low Doses ◽  
Serum Lh ◽  
Oestradiol Benzoate ◽  
Adult Male Rat

ABSTRACT The influence of treatment with various doses of testosterone propionate, 5α-dihydrotestosterone propionate or oestradiol benzoate on serum levels of LH and FSH (measured by radioimmunoassay) and on weights of ventral prostates and seminal vesicles was investigated in castrated, adult, male rats. For depression of the high, castrate levels of serum gonadotrophins with either of these steroid esters, the inhibition curves were different for LH and for FSH. Serum LH was kept at levels encountered in intact, adult, male rats by lower doses of steroid ester than was serum FSH. Oestradiol benzoate was the most potent suppressor of the serum gonadotrophins among the steroid esters tested, testosterone propionate the least. Treatment with low doses of oestradiol benzoate, however, resulted in serum FSH levels significantly above those of castrates treated with vehicle only. Finally, administration of a synthetic LH-releasing factor to testosterone propionate, 5α-dihydrotestosterone propionate or oestradiol benzoate treated, castrated, adult, male rats resulted in a further release of both LH and FSH. The latter effect was more pronounced in oestradiol benzoate treated castrates than in testosterone propionate or 5α-dihydrotestosterone propionate treated castrates.

HYPOTHALAMIC-PITUITARY-TESTICULAR SYSTEM AND ADRENOCORTICAL FUNCTION

1976 ◽  
Vol 81 (1) ◽  
pp. 198-207 ◽  
Author(s):  
H. L. Verjans ◽  
K. B. Eik-Nes
Keyword(s):  
Adrenal Gland ◽  
Blood Serum ◽  
Adult Male ◽  
Serum Levels ◽  
Male Rats ◽  
Intramuscular Administration ◽  
Adrenocortical Function ◽  
Male Rat ◽  
Pituitary Secretion ◽  
Slight Elevation

ABSTRACT Effect of intramuscular administration of ACTH or dexamethasone on blood serum levels of testosterone, LH and FSH was examined in intact and castrated, adult, male rats. Six IU ACTH or 1 mg dexamethasone were given daily for 7 days. Corticotrophin treatment had no influence on circulating testosterone, LH and FSH in intact or castrated male rats. Dexamethasone administration resulted in a slight elevation of serum FSH in intact animals but not in castrates. LH and testosterone remained normal in both intact and castrated animals injected with dexamethasone. Under our conditions of study the secretions from the adrenal gland appear to be insignificant for the regulation of pituitary secretion of gonadotrophins in the male rat.

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 In vitro pituitary and testicular effects of the leptin-related synthetic peptide leptin(116-130) amide involve actions both similar to and distinct from those of the native leptin molecule in the adult rat

2000 ◽  
pp. 406-410 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
LC Gonzalez ◽  
J Navarro ◽  
C Dieguez ◽  
...  
Keyword(s):  
Body Weight ◽  
Adult Male ◽  
Body Weight Gain ◽  
Biologically Active ◽  
Male Rats ◽  
Male Rat ◽  
Gh Secretion ◽  
Adult Rat ◽  
Testosterone Secretion

The obese gene (ob) product, leptin, has recently emerged as a key element in body weight homeostasis, neuroendocrine function and fertility. Identification of biologically active, readily synthesized fragments of the leptin molecule has drawn considerable attention, as they may provide a powerful tool for detailed characterization of the biological actions of leptin in different experimental settings. Recently, a fragment of mouse leptin protein comprising amino acids 116-130, termed leptin(116-130) amide, was shown to mimic the effects of the native molecule in terms of body weight gain and food intake, and to elicit LH and prolactin (PRL) secretion in vivo. As a continuation of our previous experimental work, the present study reports on the effects of leptin(116-130) amide on basal and stimulated testosterone secretion by adult rat testis in vitro. In addition, a comparison of the effects of human recombinant leptin and leptin(116-130) amide at the pituitary level on the patterns of LH, FSH, PRL and GH secretion is presented. As reported previously by our group, human recombinant leptin(10(-9)-10(-7)M) significantly inhibited both basal and human chorionic gonadotrophin (hCG)-stimulated testosterone secretion in vitro. Similarly, incubation of testicular tissue in the presence of increasing concentrations of leptin(116-130) amide (10(-9)-10(-5)M) resulted in a dose-dependent inhibition of basal and hCG-stimulated testosterone secretion; a reduction that was significant from a dose of 10(-7)M upwards. In addition, leptin(116-130) amide, at all doses tested (10(-9)-10(-5)M), significantly decreased LH and FSH secretion by incubated hemi-pituitaries from adult male rats. In contrast, in the same experimental protocol, recombinant leptin(10(-9)-10(-7)M) was ineffective in modulating LH and FSH release. Finally, neither recombinant leptin nor leptin(116-130) amide were able to change basal PRL and GH secretion in vitro. Our results confirm the ability of leptin, acting at the testicular level, to inhibit testosterone secretion, and map the effect to a domain of the leptin molecule that lies between amino acid residues 116 and 130. In addition, we provide evidence for a direct inhibitory action of leptin(116-130) amide on pituitary LH and FSH secretion, a phenomenon not observed for the native leptin molecule, in the adult male rat.

EFFECTS OF 17β-HYDROXY-4-ANDROSTEN-19-OL-3-ONE (19-HYDROXYTESTOSTERONE) AND 5α-ANDROSTAN-17β-OL-3-ONE (DIHYDROTESTOSTERONE) ON ASPECTS OF SEXUAL BEHAVIOUR IN CASTRATED MALE RATS

1974 ◽  
Vol 61 (1) ◽  
pp. 105-115 ◽  
Author(s):  
R. F. PARROTT
Keyword(s):  
Adult Male ◽  
Sexual Behaviour ◽  
Testosterone Propionate ◽  
Male Rats ◽  
Organ Weights ◽  
Refractory Periods ◽  
Peripheral Effect ◽  
Rate Of Decline ◽  
The Brain ◽  
Experienced Adult

SUMMARY The ability of 19-hydroxytestosterone propionate (150 μg/day) to maintain sexual behaviour, accessory organ weights and the number of penile spines in experienced adult male rats in the 5 weeks after castration was compared with intact males and castrated animals receiving testosterone propionate (75 μg/day) or oil treatment. In a second experiment a group of male rats receiving dihydrotestosterone propionate (150 μg/day) was also included. 19-Hydroxytestosterone did not maintain ejaculatory performance but animals that ejaculated had refractory periods similar to those in intact and testosterone-treated groups. Dihydrotestosterone, however, slowed the rate of decline of ejaculatory performance but the refractory periods were comparable to those in castrated controls. The former action of dihydrotestosterone was attributed to its stimulatory effect on peripheral structures, especially the penile spines. 19-Hydroxytestosterone was shown to have no peripheral effect at doses up to 1800 μg every other day. The results are discussed in terms of a theory of testosterone action involving aromatization in the brain and 5α-reduction peripherally.

scholarly journals Testosterone-dependent variations in plasma and intrapituitary corticosteroid binding globulin and stress hypothalamic-pituitary-adrenal activity in the male rat

2004 ◽  
Vol 181 (2) ◽  
pp. 223-231 ◽  
Author(s):  
V Viau ◽  
MJ Meaney
Keyword(s):  
Feedback Regulation ◽  
High Plasma ◽  
Male Rats ◽  
Testosterone Replacement ◽  
Male Rat ◽  
Plasma Testosterone ◽  
Hypothalamic Pituitary Adrenal ◽  
Corticosteroid Binding Globulin ◽  
Low Testosterone

Hypothalamic-pituitary-adrenal (HPA) activity is governed by glucocorticoid negative feedback and the magnitude of this signal is determined, in part, by variations in plasma corticosteroid-binding globulin (CBG) capacity. Here, in gonadectomized male rats we examine the extent to which different testosterone replacement levels impact on CBG and HPA function. Compared with gonadectomized rats with low testosterone replacement ( approximately 2 ng/ml), plasma adrenocorticotropin and beta-endorphin/beta-lipotropin responses to restraint stress were reduced in gonadectomized rats with high testosterone replacement ( approximately 5 ng/ml). Plasma CBG levels also varied negatively as a function of testosterone concentration. Moreover, glucocorticoid receptor binding in the liver was elevated by higher testosterone replacement, suggesting that testosterone acts to enhance glucocorticoid suppression of CBG synthesis. Since pituitary intracellular CBG (or transcortin) is derived from plasma, this prompted us to examine whether transcortin binding was similarly responsive to different testosterone replacement levels. Transcortin binding was lower in gonadectomized rats with high plasma testosterone replacement ( approximately 7 ng/ml) than in gonadectomized rats with low testosterone replacement ( approximately 2 ng/ml). This testosterone-dependent decrease in pituitary transcortin was associated, in vitro, with an enhanced nuclear uptake of corticosterone. These findings indicate that the inhibitory effects of testosterone on corticotrope responses to stress may be linked to decrements in plasma and intrapituitary CBG. This could permit greater access of corticosterone to its receptors and enhance glucocorticoid feedback regulation of ACTH release and/or proopiomelanocortin processing.

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