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.

THE EFFECTS OF ORCHIDECTOMY AND TESTOSTERONE PROPIONATE INJECTION ON PEPTIDASE ACTIVITY IN THE MALE RAT HYPOTHALAMUS

1973 ◽  
Vol 72 (1) ◽  
pp. 1-8 ◽  
Author(s):  
E. C. Griffiths ◽  
K. C. Hooper
Keyword(s):  
Luteinizing Hormone ◽  
Testosterone Propionate ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Peptidase Activity ◽  
Female Rat ◽  
Similar Relationship ◽  
Testosterone Treatment ◽  
Rat Hypothalamus

ABSTRACT It has previously been shown that the activity of certain peptidases in the female rat hypothalamus is related to the release of luteinizing hormone releasing factor from the tissue (Griffiths & Hooper 1972a). The activity of these enzymes was investigated after orchidectomy and testosterone propionate injection to determine if a similar relationship exists in male rats. The depression in supernatant activity following orchidectomy and the elevation after testosterone treatment are interpreted as confirming this, and it is proposed that alterations in peptidase activity may be used as an index of gonadotrophin release in male as well as in female rats.

EFFECT OF NEONATAL ADMINISTRATION OF STEROIDS OR GONADECTOMY UPON OESTRADIOL-INDUCED LUTEINIZING HORMONE RELEASE IN RATS OF BOTH SEXES

1980 ◽  
Vol 85 (1) ◽  
pp. 69-74 ◽  
Author(s):  
F. GOGAN ◽  
I. A. BEATTIE ◽  
M. HERY ◽  
E. LAPLANTE ◽  
C. KORDON
Keyword(s):  
Luteinizing Hormone ◽  
Sexual Differentiation ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Hormone Release ◽  
Adult Rats ◽  
Luteinizing Hormone Release ◽  
Neonatal Administration ◽  
Lh Secretion

SUMMARY Implantation of oestradiol into adult rats of both sexes induced different patterns of LH secretion depending on the time at which gonadectomy or testosterone injection were performed. Castration 2 h after birth allowed an LH peak to occur daily at 18.00 h, but its amplitude was lower than that of adult gonadectomized female rats treated with oestradiol. Castration 24 h after birth elicited two kinds of response; a circadian discharge of LH lower than that of male rats gonadectomized 2 h after birth or a steady low level of LH. The LH rhythmicity induced by implantation of oestradiol was not seen after castration at 8 weeks of age. Neonatal administration of testosterone to female rats prevented the LH peak induced by oestradiol that was seen in adult ovariectomized rats. Neonatal or adult ovariectomy did not interfere with the rhythmical response of LH after implantation of oestradiol. Thus, it is concluded that sexual differentiation of the hypothalamus is primarily of masculine origin.

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.

IMPORTANCE OF PERINATAL TESTOSTERONE IN SEXUAL DIFFERENTIATION IN THE MALE RAT

1981 ◽  
Vol 91 (1) ◽  
pp. 75-79 ◽  
Author(s):  
F. GOGAN ◽  
A. SLAMA ◽  
B. BIZZINI-KOUTZNETZOVA ◽  
F. DRAY ◽  
C. KORDON
Keyword(s):  
Sexual Differentiation ◽  
Critical Period ◽  
Rapid Decrease ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Fetal Period ◽  
Testosterone Secretion

Testosterone secretion in the male rat was high during the late fetal and immediate postnatal periods. It then showed a rapid decrease 3 h after birth and remained low until puberty. Male rats from mothers given daily injections of an antibody to testosterone during the week before delivery displayed an LH peak when they were adult, orchidectomized and implanted with oestradiol. However, the amplitude of the peak was far smaller than in female rats from the same mothers treated in the same manner. Thus, the critical period during which testosterone triggers hypothalamic sexual differentiation is very close to birth, possibly starting at the end of the fetal period.

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 Reproductive toxicity of triazole fungicides cyproconazole and epoxiconazole when exposed to male and female wistar rats during gametogenesis

2021 ◽  
Vol 54 (1) ◽  
pp. 52-61
Author(s):  
NR Shepelskaya ◽  
YaV Kolyanchuk
Keyword(s):  
Body Weight ◽  
Reproductive Toxicity ◽  
Reproductive Function ◽  
Female Rats ◽  
Male Rats ◽  
Corpora Lutea ◽  
Disruptive Effect ◽  
Male And Female ◽  
Two Samples ◽  
Adverse Effect Level

Aim. Studying the effect of generic pesticides cyproconazole (98 %) and two samples of epoxiconazole (epoxiconazole 1 — 95,75 % and epoxiconazole 2 — 98,7 %) on the reproductive system of male and female Wistar Han rats at the level of the organism when exposed during gametogenesis, identification and characterization of their hazard, as well as assessment of the risk of reproductive toxicity of these compounds. Materials and Methods. The test samples were administered daily (5 days a week) by oral gavage at doses of 0.2 and 2.0 mg/kg for cyproconazole and 0.5 and 2.0 mg/kg for epoxiconazoles during 11 weeks for males, and 10 weeks for females. Also, there were kept intact males and females, intended for crossover mating with experimental animals. After the end of the exposure, functional indicators of the state of the gonads and the ability of animals to reproduce offspring were studied. The duration and the frequency of each stage of the estrous cycle in female rats and the number of motile sperm, the total amount of sperm and the number of abnormal forms of germ cells of the male rats were studied. The reproductive function state in females was evaluated on day 20th of pregnancy. Thereby the number of corpora lutea in the ovaries, number of alive, dead and resorbed foetuses and embryos, the foetus weight, total weight of litters were registered. The studies were carried out in accordance with the recommendations of the Bioethics Commission and the Centre’s standard operating procedures, developed in accordance with the recommendations and requirements of Good Laboratory Practice (GLP). Conclusions. Test substances at a maximum dose of 2.0 mg/kg of body weight have reproductive toxicity and endocrine-disruptive effect, exerting a significant antiandrogenic effect on males and antiestrogenic effect on female rats. No-observed-adverse-effect-level (NOАEL) for gonadal and reproductive toxicity for male and female Wistar Han rats were established. They are 0.2 mg/kg body weight for cyproconazole and 0.5 mg/kg body weight for epoxiconazole. Key Words: azole fungicides, cyproconazole, epoxiconazole, reproductive toxicity, antiandrogenic and antiestrogenic effects, Wistar Han rats.

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 Comparative effects of testosterone propionate, oestradiol benzoate, ICI 182,780, tamoxifen and raloxifene on hypothalamic differentiation in the female rat

2002 ◽  
Vol 172 (3) ◽  
pp. 441-448 ◽  
Author(s):  
L Pinilla ◽  
ML Barreiro ◽  
LC Gonzalez ◽  
M Tena-Sempere ◽  
E Aguilar
Keyword(s):  
Positive Feedback ◽  
Testosterone Propionate ◽  
Reproductive Function ◽  
Female Rats ◽  
Normal Brain ◽  
Female Rat ◽  
Vaginal Opening ◽  
Ici 182,780 ◽  
Oestradiol Benzoate ◽  
Normal Differentiation

Hypothalamic differentiation in the female rat during the neonatal period is critically dependent on the steroid milieu, as permanent changes in reproductive function are observed after administration of oestradiol and testosterone during such a critical stage. Selective oestrogen modulators (SERMs) constitute a family of drugs that, depending on the tissue, are able to exert oestrogenic or antioestrogenic actions. The present experiments were conducted to analyse whether the SERMs, tamoxifen and raloxifene, can cause oestrogenic actions during the hypothalamic differentiation period. Postnatal female rats were injected between days 1 and 5 with 100 microg/day tamoxifen, raloxifene or ICI 182,780 (a pure antioestrogen). Other groups of animals were injected on day 1 of age with 100 microg oestradiol benzoate (OeB) or 1.25 mg testosterone propionate (TP) alone or in combination with raloxifene (500 microg/day between days 1 and 5). In all experimental groups, the age, body weight and concentrations of serum gonadotrophins at vaginal opening were recorded, whereas vaginal cyclicity and the negative and positive feedback between oestradiol and LH were monitored in adulthood. The results obtained confirmed the ability of high doses of OeB or TP to alter the normal differentiation of the brain permanently. They also reinforced the hypothesis that oestrogens are also necessary for normal brain differentiation in female rats because administration of a pure antioestrogen, such as ICI 182,780 permanently altered the function of the reproductive axis. In addition, our data provided evidence for different actions of the two SERMs under analysis (raloxifene and tamoxifen) upon peripheral targets, as raloxifene advanced vaginal opening whereas tamoxifen did not. In contrast, their actions on brain differentiation appeared similar and analogous to those obtained after neonatal administration of oestradiol, as evidenced by vaginal acyclicity, ovarian atrophy, sterility and abolition of negative and positive feedback between oestradiol and LH, thus suggesting an oestrogenic action of these SERMs on hypothalamic differentiation. Moreover, the oestrogenic activity of raloxifene was supported by its inability to block the effects of OeB and TP administered neonatally. In conclusion, the present results indicated that the SERMs, tamoxifen and raloxifene, exert an oestrogen-like effect upon hypothalamic differentiation of the neonatal female rat.

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

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