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.

scholarly journals Neurons and Glial Cells Are Added to the Female Rat Anteroventral Periventricular Nucleus During Puberty

Endocrinology ◽  
2016 ◽  
Vol 157 (6) ◽  
pp. 2393-2402 ◽  
Author(s):  
Margaret A. Mohr ◽  
Francisca L. Garcia ◽  
Lydia L. DonCarlos ◽  
Cheryl L. Sisk
Keyword(s):  
Cell Proliferation ◽  
Sex Difference ◽  
Positive Feedback ◽  
Reproductive Function ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Periventricular Nucleus ◽  
Mature Neurons ◽  
Female Specific

The anteroventral periventricular nucleus (AVPV) orchestrates the neuroendocrine-positive feedback response that triggers ovulation in female rodents. The AVPV is larger and more cell-dense in females than in males, and during puberty, only females develop the capacity to show a positive feedback response. We previously reported a potential new mechanism to explain this female-specific gain of function during puberty, namely a female-biased sex difference in the pubertal addition of new cells to the rat AVPV. Here we first asked whether this sex difference is due to greater cell proliferation and/or survival in females. Female and male rats received the cell birthdate marker 5-bromo-2′-deoxyuridine (BrdU; 200 mg/kg, ip) on postnatal day (P) 30; brains were collected at short and long intervals after BrdU administration to assess cell proliferation and survival, respectively. Overall, females had more BrdU-immunoreactive cells in the AVPV than did males, with no sex differences in the rate of cell attrition over time. Thus, the sex difference in pubertal addition of AVPV cells appears to be due to greater cell proliferation in females. Next, to determine the phenotype of pubertally born AVPV cells, daily BrdU injections were given to female rats on P28–56, and tissue was collected on P77 to assess colocalization of BrdU and markers for mature neurons or glia. Of the pubertally born AVPV cells, approximately 15% differentiated into neurons, approximately 19% into astrocytes, and approximately 23% into microglia. Thus, both neuro- and gliogenesis occur in the pubertal female rat AVPV and potentially contribute to maturation of female reproductive function.

GONADOTROPHIN PATTERNS IN MALE AND FEMALE RATS:

1968 ◽  
Vol 58 (4) ◽  
pp. 600-612 ◽  
Author(s):  
Robert Boyd ◽  
Donald C. Johnson
Keyword(s):  
Ascorbic Acid ◽  
Testosterone Propionate ◽  
Female Rats ◽  
Female Rat ◽  
Feedback Effects ◽  
Male And Female ◽  
Prostate Weight ◽  
Male And Female Rats ◽  
Males And Females ◽  
Normal Males

ABSTRACT The effects of various doses of testosterone propionate (TP) upon the release of luteinizing hormone (LH or ICSH) from the hypophysis of a gonadectomized male or female rat were compared. Prostate weight in hypophysectomized male parabiotic partners was used to evaluate the quantity of circulating LH. Hypophyseal LH was measured by the ovarian ascorbic acid depletion method. Males castrated when 45 days old secreted significantly more LH and had three times the amount of pituitary LH as ovariectomized females. Administration of 25 μg TP daily reduced the amount of LH in the plasma, and increased the amount in the pituitary gland, in both sexes. Treatment with 50 μg caused a further reduction in plasma LH in males, but not in females, while pituitary levels in both were equal to that of their respective controls. LH fell to the same low level in partners of males or females receiving 100 μg TP. When gonadectomized at 39 days, males and females had the same amount of plasma LH, but males had more stored hormone. Pituitary levels were unchanged from controls following treatment with 12.5, 25 or 50 μg TP daily, but plasma values dropped an equal amount in both sexes with the latter two doses. Androgenized males or females, gonadectomized when 39 days old, were very sensitive to the effects of TP and plasma LH was significantly reduced with 12.5 μg daily. Pituitary LH in androgenized males was higher than that of normal males but was reduced to normal by small amounts of TP. The amount of stored LH in androgenized females was not different from that of normal females and it was unchanged by any dose of TP tested. Results are consistent with the conclusion that the male hypothalamic-hypophyseal axis is at least as sensitive as the female axis to the negative feedback effects of TP. Androgenization increases the sensitivity to TP in both males and females.

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 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).

EFFECTS OF OESTRADIOL-17β, OESTRADIOL BENZOATE AND THE SYNTHETIC OESTROGEN RU 2858 ON SEXUAL DIFFERENTIATION IN THE NEONATAL FEMALE RAT

1975 ◽  
Vol 67 (3) ◽  
pp. 419-424 ◽  
Author(s):  
CYNTHIA DOUGHTY ◽  
JANET E. BOOTH ◽  
P. G. McDONALD ◽  
R. F. PARROTT
Keyword(s):  
Rat Brain ◽  
Sexual Differentiation ◽  
Neonatal Rat ◽  
Female Rats ◽  
Sexual Receptivity ◽  
Female Rat ◽  
Neonatal Rats ◽  
Oestradiol Benzoate ◽  
Ovarian Cyclicity ◽  
Neonatal Rat Brain

SUMMARY Groups of neonatal female rats were treated for the first 5 days of life with oestradiol-17β, oestradiol benzoate or a synthetic oestrogen, 11β-methoxy-17-ethynyl-1,3,5(10)-oestratriene-3,17β-diol (RU 2858), in daily doses ranging from 0·5 to 1000 ng. Oestradiol-17β had no effect on adult ovarian cyclicity or sexual receptivity after ovariectomy and oestrogen + progesterone treatment. Ovarian cyclicity was prevented by 100 ng or more oestradiol benzoate/day, and by all doses of RU 2858. Only rats receiving 50 ng oestradiol benzoate/ day or 0·5 ng RU 2858/day showed normal receptivity. The defeminizing action of RU 2858 was at least 100 times greater than that of oestradiol benzoate; it is suggested that this greater potency is due to the low affinity of RU 2858 for the oestradiol-binding protein in the plasma of neonatal rats. These results indicate that defeminization of the neonatal rat brain can be induced by physiological amounts of oestrogen, and are discussed with reference to the action of testosterone.

Effect of exercise on the onset of puberty, gonadotropins, and ovarian inhibin

1987 ◽  
Vol 63 (3) ◽  
pp. 1165-1173 ◽  
Author(s):  
J. Pellerin-Massicotte ◽  
G. R. Brisson ◽  
C. St-Pierre ◽  
P. Rioux ◽  
D. Rajotte
Keyword(s):  
Luteinizing Hormone ◽  
Exercise Program ◽  
Reproductive Function ◽  
The Body ◽  
Female Rats ◽  
Vaginal Opening ◽  
Adult Rats ◽  
Middle Point ◽  
Critical Weight ◽  
Ovarian Inhibin

Swimming 6 h/day from 11 days of age led to a significant delay of the onset of puberty of female rats compared with the sedentary group. Rats who were in contact with water but without the energy expenditure due to exercise (paddlers) had their vaginal opening in a middle point between control and exercising rats. Vaginal opening occurred at different ages but at a same body weight. Exercise and stress led to a marked decrease of the body weights between 19 and 40 days of age. Serum luteinizing hormone and follicle-stimulating hormone were increased with the exercise program at 30 days of age, whereas no significant differences between groups in serum gonadotropins were observed at 50 days of age. Only the anterior pituitary luteinizing hormone content was increased by exercise in adult rats. Total ovarian proteins were significantly reduced by stress and to a greater degree by exercise. Ovarian inhibin activity is not modified by exercise at 30 days of age, whereas it increased significantly in the exercising group at 50 days of age and to a lesser degree in paddlers. It is therefore suggested that the onset of puberty in rats is dependent on a critical weight and that exercise and stress can delay the onset of puberty. This delay could be explained by a deficiency of hormonal maturational process while exercising until sexual maturity alters the inhibin activity, which suggests that inhibin could play a major role for the normal reproductive function and this could possibly explain the menstrual disturbances in the female athlete.

SERUM CORTICOSTERONE IN RATS WITH DELAYED ANOVULATION

1976 ◽  
Vol 71 (1) ◽  
pp. 31-36 ◽  
Author(s):  
JUDITH A. RAMALEY
Keyword(s):  
Low Dose ◽  
Testosterone Propionate ◽  
Ovariectomized Rats ◽  
Tube Length ◽  
Blood Levels ◽  
Early Exposure ◽  
Vaginal Opening ◽  
Adrenal System ◽  
Oestradiol Benzoate ◽  
Intact Rats

SUMMARY The purpose of this study was to investigate adrenal function in rats during the development of persistent oestrus to determine whether a change in blood levels of corticosterone would precede or coincide with the onset of infertility. The syndrome of delayed persistent oestrus and anovulation was induced by administration of a low dose (10 μg) of testosterone propionate (TP) at 5 days of age. Control animals were handled without injection or received the vehicle (sesame oil) only. Half of each group was ovariectomized at weaning and received Silastic implants of either oestradiol benzoate (OB) or cholesterol, 3 mm tube length/100 g body weight. Intact rats given the low TP dose showed precocious vaginal opening (27·3 ± 2·1 days v. 37·6 ± 2·4 (s.e.m.) days in unhandled controls) and ovulated within 2 days. Persistent vaginal cornification developed in 22 out of 26 rats by 75 days of age. The TP-treated rats had higher corticosterone values than the controls and did not show a further increase after OB implantation. Cholesterol implantation depressed corticosterone levels in the TP-treated rats. The effects of the low TP dose were not dependent upon gonadal function since they persisted in ovariectomized rats. The results suggest that early exposure to androgen can modify the sensitivity of the adrenal system to oestrogen, and can also lead to persistently high values of corticosterone which are not depressed by ovariectomy. These changes precede the onset of persistent oestrus.

THE EFFECT OF HEPATECTOMY AND SEX HORMONES ON THE PSEUDOCHOLINESTERASE ACTIVITY IN LIVER AND SERUM OF THE RAT

1970 ◽  
Vol 65 (1) ◽  
pp. 184-192 ◽  
Author(s):  
R. S. Leeuwin ◽  
E. Th. Groenewoud
Keyword(s):  
Sex Hormones ◽  
Testosterone Propionate ◽  
Marked Decrease ◽  
Normal Values ◽  
Female Rats ◽  
Slow Increase ◽  
Male And Female Rats ◽  
Oestradiol Benzoate ◽  
Synthetic Capacity ◽  
Low Activity

ABSTRACT A study was made of the combined effects of hepatectomy, castration and treatment with sex hormones on the pseudocholinesterase activity in liver and serum of male and female rats. Hepatectomy in normal rats results in a sharp decline of the pseudocholinesterase activity, subsequently followed in females by a rapid increase to normal values and in males by a very slow increase. Hepatectomy in castrated rats also causes a marked decrease of the pseudocholinesterase activity, but the pseudocholinesterase activity remains at a relatively low level, in both castrated females and castrated males. Daily treatment of castrated-hepatectomized females with oestradiol-benzoate, either immediately or nine days after hepatectomy induces a gradual restoration of the enzyme activity to and above the normal castrate level. When castrated-hepatectomized males are treated daily with testosterone-propionate the extremely low activity may even be depressed further. These experiments once again stress the important role played by the liver and by sex hormones in the synthesis of the enzyme pseudocholinesterase. There was no evidence from our experiments that the steroid hormones affect the speed of regeneration of the liver as a whole. From this it must be decided that they only affect the restoration of the synthetic capacity for pseudocholinesterase. In all experiments the changes in liver pseudocholinesterase activity were reflected in the serum activity.

DISSOCIATION IN THE REGULATION OF LUTEINIZING HORMONE AND FOLLICLE-STIMULATING HORMONE IN A HYPERPROLACTINAEMIC RAT MODEL: INTERRELATIONSHIPS BETWEEN GONADOTROPHIN AND PROLACTIN CONTROL

1981 ◽  
Vol 90 (1) ◽  
pp. 41-51 ◽  
Author(s):  
J. A. F. TRESGUERRES ◽  
A. I. ESQUIFINO
Keyword(s):  
Positive Feedback ◽  
Follicle Stimulating Hormone ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Oestradiol Benzoate ◽  
Female Wistar Rats ◽  
Pituitary Glands ◽  
Lh Rh ◽  
Lh Releasing Hormone

Male and female Wistar rats were made hyperprolactinaemic by grafting two pituitary glands of litter-mate donors under the kidney capsule at 30 days of age. Other animals were sham-operated at the same age to serve as controls. Plasma levels of prolactin, LH and FSH were measured by double-antibody radioimmunoassay. Basal preoperative prolactin levels of ∼ 10 ng/ml increased after the transplantation in both male and female rats, reaching values of ∼ 180 ng/ml. Levels of LH were significantly reduced in these hyperprolactinaemic rats, whereas an increase in FSH values was seen. After administration of LH releasing hormone (LH-RH) a reduced LH response was seen but there was no response of FSH to LH-RH or even a decrease in FSH values. Prolactin levels were also reduced by LH-RH injection. Although an increase in prolactin levels was observed in control animals after a challenge with oestradiol benzoate, reduced increments were seen in experimental animals. The positive feedback effect of oestradiol benzoate on LH in females was reduced in pituitary-grafted rats but a potentiation of the FSH positive feedback could be clearly detected. This study suggests a dissociation of LH and FSH regulation in hyperprolactinaemia.

scholarly journals Oestrogens regulate pituitary alpha2,3-sialyltransferase messenger ribonucleic acid levels in the female rat

1999 ◽  
Vol 23 (2) ◽  
pp. 153-165 ◽  
Author(s):  
P Damian-Matsumura ◽  
V Zaga ◽  
A Maldonado ◽  
C Sanchez-Hernandez ◽  
C Timossi ◽  
...  
Keyword(s):  
Anterior Pituitary ◽  
Cdna Probe ◽  
Ovariectomized Rats ◽  
Molecular Forms ◽  
Northern Blot Hybridization ◽  
Mrna Levels ◽  
Female Rat ◽  
Messenger Ribonucleic Acid ◽  
Ici 182,780 ◽  
Oestradiol Benzoate

Follicle-stimulating hormone (FSH) is synthesized by the anterior pituitary gland in multiple molecular forms. Increased acidic/sialylated FSH charge isoforms are associated with conditions characterized by a low oestrogen output. In the present study, we analysed the dynamics of the changes in mRNA levels of the enzyme Galbeta1,3[4]GlcNAc alpha2,3-sialyltransferase (2,3-STase) (one of the enzymes that incorporate sialic acid residues into the FSH molecule) in intact and ovariectomized rats. The anterior pituitaries of 4-day regularly cyclic adult female Wistar rats were obtained at 1000 h on the days of pro-oestrus (P), oestrus (O), dioestrus 1 (D1) and dioestrus 2 (D2), at 0200 h, 1400 h, 1800 h and 2200 h on D1, at 1800 h on day of O and at 1000 h after 7, 14, 21, 28 and 45 days of oophorectomy performed on the morning of P. Total RNA was isolated from each gland and the 2,3-STase levels were measured by Northern blot hybridization analysis employing a 346-base pair cDNA probe encoding for a non-conserved amino acid sequence of the catalytic domain of the enzyme. Maximal levels of the enzyme mRNA were detected at 1000 h on D1; thereafter, they progressively decreased by 60% during the ensuing 24 h, reaching the lowest concentration values (26% of the maximally observed level on D1) at 1000 h on day of P and remaining unchanged during the morning of O. Administration of the potent oestradiol receptor antagonist ICI 182,780 at 1000 h on D1 completely reverted the time-dependent decrease in 2,3-STase mRNA levels observed during the afternoon of D1, whereas oestradiol benzoate administered at 1000 h on day of O significantly reduced the enzyme mRNA levels (to 21% of the levels detected in vehicle-treated controls). In ovariectomized rats, the alpha2,3-STase mRNA progressively increased from day 21 to day 45 post castration. Administration of oestradiol benzoate on day 28 after oophorectomy significantly reduced the 2,3-STase mRNA levels (to 36% of the levels detected in vehicle-injected controls); ICI 182,780 partially counteracted this oestradiol-mediated effect. The dynamics of these changes in 2,3-STase mRNA levels partially correlated with changes in the relative abundance of the FSH charge isoforms separated by preparative chromatofocusing of anterior pituitary extracts, particularly in glands obtained during the morning of P and O. These data demonstrate for the first time that pituitary 2,3-STase is a hormonally-regulated enzyme and that the changes in transcription and/or stability of its mRNA may be involved, in part, in the post-translational processing of the FSH molecule during certain physiological conditions.

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