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).

RELATIONSHIP BETWEEN THE PITUITARY GLAND AND GONADAL STEROIDS: INVOLVEMENT OF A HYPOPHYSIAL FACTOR IN REDUCED α2u-GLOBULIN AND INCREASED TRANSCORTIN CONCENTRATIONS IN RAT SERUM

1978 ◽  
Vol 78 (1) ◽  
pp. 31-38 ◽  
Author(s):  
G. VANDOREN ◽  
H. VAN BAELEN ◽  
G. VERHOEVEN ◽  
P. DE MOOR
Keyword(s):  
Pituitary Gland ◽  
Testosterone Propionate ◽  
Single Injection ◽  
Prolactin Secretion ◽  
Female Rats ◽  
Male Rats ◽  
Rat Serum ◽  
Mediated Effects ◽  
Male And Female Rats ◽  
Oestradiol Benzoate

Evidence is presented that the level of α2u-globulin in the serum of male rats depends, at least in part, on neonatal androgens. After castration of adult animals the concentration of this protein falls but remains measurable, whereas in intact or ovariectomized female rats α2u-globulin cannot be detected. Moreover, α2u-globulin is found in adult male and female rats gonadectomized at birth and treated with a single injection of testosterone propionate immediately thereafter. The mechanism by which neonatal androgens increase the concentration of α2u-globulin has been investigated. Transplantation of a supplementary pituitary gland under the renal capsule of male rats resulted in reduced levels of α2u-globulin and increased levels of transcortin. The changes discussed here were observed only in those animals in which the transplant was functional and they were amplified or reversed by modulators of prolactin secretion such as oestrogens or bromocriptine respectively. The hypothesis is advanced that neonatal androgens stimulate the production of a hypothalamic inhibitory factor that controls the secretion of prolactin, or another hypophysial hormone subjected to similar neuroendocrine control. Measurements in gonadectomized animals and in rats receiving both oestradiol benzoate and bromocriptine indicate that, besides these pituitary-mediated effects, both oestrogens and androgens exert direct effects on the level of α2u-globulin.

LORDOSIS BEHAVIOUR IN MALE, FEMALE AND ANDROGENIZED FEMALE RATS

1976 ◽  
Vol 70 (3) ◽  
pp. 409-420 ◽  
Author(s):  
P. SÖDERSTEN
Keyword(s):  
Testosterone Propionate ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Normal Female ◽  
Adult Rats ◽  
Oestradiol Benzoate ◽  
Series Of Experiments ◽  
Lordosis Behaviour ◽  
Dose Dependent

SUMMARY Sex differences in the lordosis response of adult rats to ovarian hormones were studied in a series of experiments. Male rats were less sensitive to oestradiol benzoate (OB, a single injection of 10, 100 or 1000 μg/kg or seven daily injections of 2, 10 or 50 μg/kg) than were female rats. Oestradiol benzoate-primed (10 μg/kg) female, but not male, rats showed dose-dependent responses to progesterone (0·4, 2·0 or 10·0 mg/kg). Male rats responded clearly to progesterone (2 mg/rat) only when primed with a high dose of OB (100 μg/rat). Display of the whole pattern of female sexual behaviour was induced in male rats by treatment with 100 μg OB and 2 mg progesterone. Female rats treated with 1 mg testosterone propionate (TP) on day 4 of life, ovariectomized as adults and tested under the same endocrine conditions as the rats described above, retained behavioural OB sensitivity but responded poorly to progesterone. Evidence is presented that ovarian secretions during development significantly modify the response of neonatally TP-treated and normal female rats to OB in adulthood.

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

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.

THE EFFECTS OF SEX STEROIDS ON THE PROLACTIN CONTENT OF HYPOPHYSES AND SERUM IN RATS

1963 ◽  
Vol 43 (1) ◽  
pp. 137-146 ◽  
Author(s):  
O. L. Wolthuis
Keyword(s):  
Sex Steroids ◽  
Testosterone Propionate ◽  
Mature Female ◽  
Mature Male ◽  
Female Rats ◽  
Male Rats ◽  
List Type ◽  
Oestradiol Benzoate ◽  
Prolactin Content ◽  
Pituitary Prolactin

ABSTRACT Prolactin determinations have been carried out on the hypophyses and serum of rats. It was found that: Hypophyses of intact mature female rats contain almost twice as much prolactin as those of mature female rats spayed two months previously. The pituitary prolactin content in these spayed female rats is virtually identical with that of intact or castrated mature male rats. Treatment of intact mature female rats with oestradiol benzoate (50 μg daily for one week) considerably increases the prolactin content in the hypophyses and serum. Treatment of spayed mature female rats with sex steroids for two weeks shows that: oestradiol benzoate (50 μg daily) increases the prolactin content in the hypophyses and serum; testosterone propionate (2 mg daily) also increases the prolactin content in the hypophyses and serum, although the increases found were smaller than those obtained with the above-mentioned dose of oestradiol; progesterone (5 mg daily) did not significantly alter the pituitary prolactin content, whereas a highly suggestive increase was found in the serum content. From the results it was concluded that: Physiological amounts of androgens do not affect the prolactin function of the hypophysis, whereas physiological amounts of oestrogens do affect it. All three sex steroids investigated increase prolactin production in and secretion from the hypophysis. A negative feedback seems to be absent.

INFLUENCE OF PROLACTIN ON THE METABOLISM OF STEROID HORMONES IN RAT LIVER AND ADRENALS

1975 ◽  
Vol 78 (3) ◽  
pp. 545-553 ◽  
Author(s):  
Jan-Åke Gustafsson ◽  
Åke Stenberg
Keyword(s):  
Microsomal Fraction ◽  
Testosterone Propionate ◽  
Reductase Activity ◽  
Hepatic Metabolism ◽  
Female Rats ◽  
Male Rats ◽  
Concomitant Treatment ◽  
Male And Female ◽  
Specific Effects ◽  
Male And Female Rats

ABSTRACT The influence of prolactin treatment on the hepatic metabolism of 4-[4-14C]androstene-3,17-dione (in the microsomal and 105 000 × g supernatant fractions) and 5α-[4-14C]androstane-3α,17β-diol (in the microsomal fraction) and on the adrenal metabolism of 4-[4-14C]androstene-3,17-dione was studied in intact and castrated male and female rats with and without concomitant treatment with testosterone propionate. Whereas prolactin gave a significant and specific decrease in the activity of adrenal 5α-reductase by about 20–30 % in both male and female rats no specific effects were noted in the metabolism of steroids in the liver. Neither did prolactin compensate for the relative androgen unresponsiveness characteristic of neonatally castrated male rats. These results suggest that prolactin does not play any significant role in mediating the recently discovered hypophyseal control of sexual differentiation of hepatic steroid metabolism in the rat whereas it may have a function in maintaining sexual differences in alrenal 5α-reductase activity.

SEX DIFFERENCES AND HORMONAL CONTROL OF TESTOSTERONE METABOLISM IN RAT PITUITARY AND BRAIN

1973 ◽  
Vol 59 (3) ◽  
pp. 605-621 ◽  
Author(s):  
CARL DENEF ◽  
CAREW MAGNUS ◽  
B. S. McEWEN
Keyword(s):  
Sex Differences ◽  
Sex Difference ◽  
Testosterone Propionate ◽  
Brain Regions ◽  
Hormonal Control ◽  
Female Rats ◽  
Male Rats ◽  
Testosterone Metabolism ◽  
Conversion Rates ◽  
Oestradiol Benzoate

SUMMARY The in-vitro conversion of testosterone to 17β-hydroxy-5α-androstan-3-one (5α-dihydrotestosterone, DHT) and 3α, 17β-dihydroxy-5α-androstane (3α-androstanediol, DIOL) in pituitary and slices of brain regions was compared between male and female rats. Intact pituitaries from male rats formed 2·5 times more DHT and 1·5 times more DIOL than those of females. A small sex difference was also detected in the hypothalamus, males again being higher than females. No sex differences could be detected in other brain regions. However, DHT formation in the brain was regionally differentiated with higher conversion rates in hypothalamus than in cortex, hippocampus, amygdala, pineal gland or cerebellum. The highest transformation, however, was found in the mid-brain. Metabolism in the pre-optic area was as low as that in the cortex. 5α-Dihydrotestosterone and DIOL formation in the pituitary increased several-fold after gonadectomy in both sexes and the sex difference disappeared. Little or no increase occurred after thyroidectomy or adrenalectomy. The increase in pituitary DHT formation after gonadectomy could be attenuated or prevented both by treatment with testosterone propionate and with oestradiol benzoate. Replacement therapy, particularly with oestradiol benzoate, gave rise to a sex difference reminiscent of that of normal animals. No significant change in pituitary DHT formation occurred in adult females which had been treated with testosterone propionate on the 4th day of life. The results suggested a close relationship between DHT formation and activity of gonadotrophin secretion, particularly at the level of the pituitary.

OESTROGEN RESPONSES OF RATS NEONATALLY STERILIZED WITH STEROIDS

1969 ◽  
Vol 45 (3) ◽  
pp. 415-420 ◽  
Author(s):  
T. R. WRENN ◽  
JOAN R. WOOD ◽  
J. BITMAN
Keyword(s):  
Testosterone Propionate ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Uterine Weight ◽  
Oestradiol Benzoate

SUMMARY At 75 days of age, female rats neonatally sterilized with oestradiol benzoate or testosterone propionate were compared with normal and ovariectomized rats with regard to their 6-hr. response to 0·2 μg. oestradiol 17β. The greatest increases in uterine weight, glucose and glycogen concentrations and per cent uterine water occurred in the ovariectomized animals. A marked oestrogen response also occurred in the animals neonatally sterilized with oestradiol benzoate. The response of the normal rats was slight, and the testosterone propionate-treated rats were the least affected. Adrenal, pituitary, and ovarian weights were found to be affected by the neonatal hormone treatments. Vaginal patency was completely inhibited in the rats injected with testosterone propionate. It is concluded that rats neonatally sterilized with steroids are much less suitable than ovariectomized animals for oestrogen assays.

scholarly journals Glutathione Conjugates of Ochratoxin a as Biomarkers of Exposure / Glutationski Konjugati Okratoksina A Kao Biomarkeri Izloženosti

2012 ◽  
Vol 63 (4) ◽  
pp. 417-427 ◽  
Author(s):  
Mariana Tozlovanu ◽  
Delphine Canadas ◽  
Annie Pfohl-Leszkowicz ◽  
Christine Frenette ◽  
Robert J. Paugh ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Rat Kidney ◽  
Female Rats ◽  
Amide Bond ◽  
Male Rats ◽  
Dark Agouti ◽  
Female Rat ◽  
Male And Female ◽  
Male And Female Rats ◽  
Liver And Kidney

AbstractIn the present study the photoreactivity of the fungal carcinogen ochratoxin A (OTA) has been utilised to generate authentic samples of reduced glutathione (GSH) and N-acetylcysteine (NAC) conjugates of the parent toxin. These conjugates, along with the nontoxic OTα, which is generated through hydrolysis of the amide bond of OTA by carboxypeptidase A, were utilised as biomarkers to study the metabolism of OTA in the liver and kidney of male and female Dark Agouti rats. Male rats are more susceptible than female rats to OTA carcinogenesis with the kidney being the target organ. Our studies show that the distribution of OTA in male and female rat kidney is not significantly different. However, the extent of OTA metabolism was greater in male than female rats. Much higher levels of OTα were detected in the liver compared to the kidney, and formation of OTα is a detoxification pathway for OTA. These findings suggest that differences in metabolism between male and female rats could provide an explanation for the higher sensitivity of male rats to OTA toxicity

Toxicological evaluation of hydroethanol leaf extract of Pupalia lappacea (Linn.) Juss. (Amaranthaceae) in rodents

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Murtala Akanji Abdullahi ◽  
Elijah Oladapo Oyinloye ◽  
Akinyinka Alabi ◽  
Aderonke Adeyinka Aderinola ◽  
Luqman Opeyemi Ogunjimi ◽  
...  
Keyword(s):  
Leaf Extract ◽  
Density Lipoprotein ◽  
Serum Testosterone ◽  
Female Rats ◽  
Male Rats ◽  
Laboratory Animals ◽  
Serum Testosterone Level ◽  
Control Group ◽  
Toxicological Evaluation ◽  
Liver And Kidney

Abstract Objectives Several studies have established the ethnobotanical benefits of Pupalia lappacea (PL) in laboratory animals without extensive toxicological evaluation of its safety profiles. Thus, an extensive toxicological investigation of sub-chronic oral administration of the hydroethanol leaf extract of P. lappacea in rodents was carried out in this study. Methods Different groups of rats were treated orally with the extract (10, 50 and 250 mg/kg) daily for 90 consecutive days. The control group received distilled water (10 mL/kg). After 90 days, some rats were left for additional 30 days without treatment for reversibility study. Blood and organs samples were collected for different evaluations at the end of study periods. Results The extract decreased the bodyweights, feeding and water intakes in female rats. PL increased the weights of the liver and kidney in male rats. PL increased the red blood cell (RBC), packed cell volume (PCV), hemoglobin (Hb), triglycerides (TRIG), cholesterol and high density lipoprotein (HDL) contents in rats. PL (250 mg/kg) significantly reduced the sperm motility and serum testosterone level. Cyto-architectural distortions of the testes, liver and spleen were visible. Conclusions The findings showed that P. lappacea is relatively safe at lower doses but cautions should be taken at higher dose.

Sign in / Sign up

Export Citation Format

Share Document