Anti-oestrogenic effects of tamoxifen on mammary gland and hypophysis in female rats

1984 ◽  
Vol 105 (3) ◽  
pp. 360-370 ◽  
Author(s):  
Stephan Götze ◽  
Yukishige Nishino ◽  
Friedmund Neumann
Keyword(s):  
Mammary Gland ◽  
Combined Treatment ◽  
Secretory Activity ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Immunoperoxidase Staining ◽  
Immunoperoxidase Technique ◽  
Basal Secretion ◽  
Whole Mount ◽  
Oestradiol Benzoate

Abstract. Adult ovariectomized rats were treated for 14 days with oestradiol benzoate (E2B) 15 μg/kg/d and oestradiol benzoate 15 μg/kg/d + progesterone (PRO) 15 mg/kg/d for induction of mammary gland parenchymal stimulation. Histological examination and whole mount preparation demonstrated that ductal growth in the mammary gland after E2B treatment was completely antagonized by tamoxifen (TAM) 0.5 mg/kg/d. Parallel DNA concentrations in the mammary gland were decreased to control levels by TAM 0.5, 5 and 15 mg/kg/d. E2B-induced hyperprolactinaemia in the forenoon (basal secretion was equally reduced by TAM 0.5, 5 and 15 mg/kg/d). In the afternoon, when prolactin (Prl) secretion is at its maximum, TAM 0.5 mg/kg/d turned out to be ineffective to abolish Prl surge, but TAM 5 and 15 mg/kg/d reduced serum Prl concentrations in a doserelated manner. Immunoperoxidase staining of Prl cells in the pars distalis of the hypophysis indicated that adaptive hypertrophy and signs of hypersecretion after E2B were abolished by TAM 5 mg/kg/d. Luteotrophic cells clearly showed cellular atrophy, regression and secretory inactivity. Maximal tubulo-alveolar mammary parenchymal stimulation in rats treated with E2B-PRO was slightly inhibited by TAM 0.5 mg/kg/d. Histology showed a small disseminated parenchymal islet. DNA concentrations only were partially decreased by the anti-oestrogen though serum Prl concentrations were found to be completely decreased to control levels. Secretory activity of Prl cells was reduced by TAM 0.5 mg/kg/d. In E2B-PRO treated rats lisuride had poor inhibitory activity on Prl levels and none on DNA concentrations in the mammary gland. Combined treatment with TAM and lisuride significantly decreased DNA concentration in the mammary gland compared to animals which received E2B-PRO. Also Prl levels were at a minimum. Histology performed on the mammary gland showed only slight tubulo- but no tubulo-alveolar activation. Luteotrophic cells in the pituitary gland stained by the immunoperoxidase technique appeared regressive, shrunken and atrophied.

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.

Dissociation between the ovarian factors controlling sexual receptivity and preovulatory secretion of LH in cyclic female rats

1987 ◽  
Vol 112 (1) ◽  
pp. 133-138 ◽  
Author(s):  
P. Södersten ◽  
P. Eneroth
Keyword(s):  
Sexual Behaviour ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Sexual Receptivity ◽  
Serum Progesterone ◽  
Lh Surge ◽  
Oestradiol Benzoate ◽  
Lh Release ◽  
Lh Secretion ◽  
Intact Rats

ABSTRACT Ovariectomy and treatment with oestradiol benzoate (10 μg OB) on the day before behavioural oestrus eliminated the preovulatory surge of LH and reduced the level of sexual receptivity on the following day. Sexual behaviour, but not the LH surge, was restored by progesterone (0·5 mg) given 18 h later. Injection of OB on the day after behavioural oestrus induced a small release of LH and normal sexual behaviour on the following day. Ovariectomy on the day after behavioural oestrus reduced the stimulatory effect of OB on sexual behaviour and eliminated its weakly stimulatory effect on LH release. Sexual behaviour, but not the small LH surge, was restored in these animals by progesterone (0·5 mg) given 18 h later. Treatment of rats ovariectomized 2 days before the day of the LH surge with implants containing oestradiol or injections of oestradiol (1 μg) induced LH surges but the amplitudes of these LH surges were much smaller than those of the normal LH surge. Treatment of intact rats with OB increased serum progesterone levels 24 h later, an effect which was eliminated by ovariectomy. Injections of LH (20 μg) into intact rats on the day after behavioural oestrus also increased serum progesterone concentrations but failed to stimulate sexual behaviour. It is suggested that OB treatment of intact rats on the day after behavioural oestrus stimulates sexual behaviour by inducing a surge of LH secretion which activates ovarian secretion of progesterone. Thus, oestrogen and progesterone but not the LH surge are essential for sexual behaviour. Whereas oestradiol and progesterone restore normal sexual behaviour in ovariectomized rats, additional ovarian factors may be required for induction of normal LH surges. J. Endocr. (1987) 112, 133–138

EFFECT OF PROLACTIN INHIBITORY AGENTS ON THE ECTOPIC ANTERIOR PITUITARY AND THE MAMMARY GLAND IN RATS

1977 ◽  
Vol 85 (2) ◽  
pp. 267-278 ◽  
Author(s):  
K.-J. Gräf ◽  
R. Horowski ◽  
M. F. El Etreby
Keyword(s):  
Mammary Gland ◽  
Anterior Pituitary ◽  
Direct Action ◽  
Mammary Glands ◽  
Female Rats ◽  
Simultaneous Administration ◽  
Dopaminergic Receptors ◽  
Oestradiol Benzoate ◽  
Biological Effectiveness ◽  
Inhibitory Agents

ABSTRACT The purpose of the present study was to investigate the biological effectiveness of two highly potent prolactin (PRL) inhibitors, lisuride hydrogen maleate (LMH) and 2-Br-α-ergocryptine (CB-154), in the absence of hypothalamic factors acting directly at the level of the anterior pituitary. Hypophysectomized female rats bearing 4 transplanted pituitaries beneath the kidney capsules were treated with oestradiol benzoate (OeB) and progesterone (P) with or without simultaneous administration of LHM or CB-154 for 22 days in order stimulate or inhibit lobulo-alveolar growth of the mammary glands. In addition to the investigation of the mammary glands by DNA determination and assessment of the histological pictures, the aim of this study was directed towards the influence of the substances tested at the level of the anterior pituitary remote from the hypothalmus. In this connection the changes in the different cells within the ectopic pituitaries as revealed by immunoenzyme-cytochemical studies were investigated. The results obtained support the classical view of a neuroendocrine regulation of mammary gland growth and the importance of oestrogens, P and PRL within this system. Both ergot derivatives LHM and CB-154 were able to antagonize the stimulatory effect of OeB combined with P on the mammary gland. With regard to the mechanism of action of LHM and CB-154 it is concluded that both substances act via a direct action on dopaminergic receptors within the ectopic anterior pituitary.

FINE STRUCTURE OF RAT PROLACTIN CELLS AFTER TREATMENT WITH A LONG ACTING DEPOT CONTRACEPTIVE

1978 ◽  
Vol 89 (2) ◽  
pp. 251-262 ◽  
Author(s):  
G. Aumüller ◽  
R. Wagner ◽  
K. J. Gräf
Keyword(s):  
Mammary Gland ◽  
Female Rats ◽  
Prolactin Cells ◽  
Stimulatory Action ◽  
Treatment Regimens ◽  
Morphological Findings ◽  
Oestradiol Benzoate ◽  
Rat Mammary Gland ◽  
Long Acting

ABSTRACT Adult intact female rats were injected with norethisterone oenanthate (NOe), with or without simultaneous administration of CB-154, or with oestradiol benzoate (OeB). The ultrastructure of prolactin (PRL) cells due to the various treatment regimens was investigated and compared with the situation found in controls. Both after treatment with NOe or NOe plus CB-154, the number of PRL cells increased and displayed various ultrastructure signs of stimulation. The determination of serum PRL levels coincides with these morphological findings. In all treated animals mammary gland DNA content was significantly increased. The results presented indicate that proliferative changes in the rat mammary gland depend predominantly on the presence of progestogenic activities additionally to PRL, whereas the effect of oestrogens was regarded as an indirect effect via their PRL-stimulatory action.

Naloxone reverses post-ejaculatory inhibition of sexual behaviour in female rats

1987 ◽  
Vol 113 (3) ◽  
pp. 429-434 ◽  
Author(s):  
G. Forsberg ◽  
I. Bednar ◽  
P. Eneroth ◽  
P. Södersten
Keyword(s):  
Sexual Behaviour ◽  
Opioid Peptide ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Sexual Receptivity ◽  
Peptide Receptor ◽  
Oestradiol Benzoate ◽  
Brain And Spinal Cord ◽  
The Brain

ABSTRACT Sexual receptivity was inhibited in ovariectomized rats treated with oestradiol benzoate (OB: two injections of 2 μg) and progesterone (0·5 mg) immediately after ejaculation by the male and restored after the end of the post-ejaculatory refractory period in the male. The post-ejaculatory inhibition of sexual receptivity was reversed by i.p. (5 mg), intracerebroventricular (50 μg) or intrathecal (50 μg) injection of the opioid peptide receptor antagonist naloxone. The concentration of serum β-endorphin-like immunoreactivity in ovariectomized rats treated with OB plus progesterone was unaltered by sexual interactions with males (18·3 ± 6·0 (s.e.m.), 26·4 ± 2·1 and 21·8 ± 6·1 pmol/l before sexual activity, after ejaculation and after the end of the post-ejaculatory interval) but reduced to non-detectable by hypophysectomy. Subcutaneous injection of 10 μg β-endorphin raised serum concentrations of β-endorphin-like immunoreactivity but did not affect the display of sexual behaviour. The behaviour was also unaffected by intracerebroventricular injection of 0·1, 0·2 or 1·0 μg β-endorphin or by injections of 0·25 μg β-endorphin in the periaqueductal central grey of the mesencephalon. The results show that ejaculation by male rats causes a transient inhibition of sexual receptivity in the female which may be dependent upon opioid peptide receptor mechanisms in the brain and spinal cord. It is unlikely that the peptide is β-endorphin. J. Endocr. (1987) 113, 429–434

INDUCTION OF SEXUAL RECEPTIVITY BY OESTRADIOL BENZOATE IN CYCLIC FEMALE RATS: INFLUENCE OF OVARIAN SECRETIONS BEFORE INJECTION OF OESTRADIOL BENZOATE

1979 ◽  
Vol 80 (3) ◽  
pp. 389-395 ◽  
Author(s):  
P. SÖDERSTEN ◽  
S. HANSEN
Keyword(s):  
Sexual Behaviour ◽  
Oestrous Cycle ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Sexual Receptivity ◽  
Behavioural Effect ◽  
Progesterone Treatment ◽  
Oestradiol Benzoate

The ability of cyclic female rats to show sexual receptivity 24 h after an injection of 2 μg oestradiol benzoate (OB) was lost 24 h after ovariectomy. Exposure of cyclic rats to anti-oestrogen (nitromophene monocitrate) implants 24 h before ovariectomy and OB treatment prevented the latter from inducing sexual receptivity within 24 h of administration. Treatment of ovariectomized rats with constant release implants filled with an oil solution of 15 μg oestradiol/ml had no behavioural effect in itself, but prepared the rats to show lordosis 24 h after administration of OB. Progesterone treatment (4 mg) induced sexual behaviour in cyclic rats on days other than that of the oestrous cycle when the rats are normally receptive. Evidence is presented that a lower level of oestradiol stimulation than that present during pro-oestrus was needed for the induction of sexual receptivity in ovariectomized rats. It is suggested that the low basal level of oestradiol which was present throughout the oestrous cycle was necessary for the induction of sexual receptivity and that an increase in oestradiol stimulation served to increase the behavioural sensitivity to progesterone.

Measurement of lipogenesis in isolated preputial gland cells of the rat and the effect of oestrogen

1986 ◽  
Vol 109 (1) ◽  
pp. 1-7 ◽  
Author(s):  
A. M. Alves ◽  
A. J. Thody ◽  
C. Fisher ◽  
S. Shuster
Keyword(s):  
Gland Cell ◽  
Lipid Synthesis ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Preputial Gland ◽  
Gland Cells ◽  
Oestradiol Benzoate ◽  
Preputial Glands ◽  
Prior Administration

ABSTRACT Lipogenesis was measured in isolated preputial gland cells of female rats after ovariectomy and after the administration of oestradiol benzoate. Ovariectomy decreased preputial gland cell lipogenesis and also altered the pattern of lipid synthesis, producing a relative decrease in the proportion of polar lipids and an increase in the proportion of 'triglycerides'. Although daily administration of 2 or 10 μg oestradiol benzoate for 7 days produced slight increases in preputial gland cell lipogenesis in ovariectomized rats, the effects were not significant. A single injection of 10 μg oestradiol benzoate, however, produced significant increases in preputial gland cell lipogenesis of ovariectomized rats at both 2 and 24 h and, moreover, at 24 h the pattern of polar lipid and triglyceride labelling was restored to normal. Prior administration of actinomycin D reduced the lipogenic effect of oestradiol benzoate. Oestradiol benzoate had little or no effect on preputial gland cell lipogenesis in male rats. These results confirm that oestrogen is able to stimulate preputial lipogenesis in female rats. Whether this action of oestrogen is related to its pheromone-producing effect on the preputial glands is not yet known. J. Endocr. (1986) 109, 1–7

EFFECT OF OVARIAN STEROIDS ON PREPUTIAL GLAND ODOURS IN THE FEMALE RAT

1978 ◽  
Vol 77 (3) ◽  
pp. 397-403 ◽  
Author(s):  
A. J. THODY ◽  
H. DIJKSTRA
Keyword(s):  
Single Injection ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Whole Body ◽  
Female Rat ◽  
Preputial Gland ◽  
Intact Female ◽  
Oestradiol Benzoate ◽  
Experienced Male

Sexually experienced male rats were used to test for whole body and preputial gland odours of female rats. The male rats clearly preferred whole body odours of intact female rats to those of preputialectomized female rats. The male rats also preferred the odour of preputial gland tissue of intact female rats to that of ovariectomized female rats and were especially attracted to the preputial gland odours of female rats in pro-oestrus and oestrus. The preputial gland odours of ovariectomized rats that had received oestradiol benzoate for 7 days were attractive to male rats, although similar treatment with progesterone was ineffective. However, a single injection of progesterone given 72 h after a single injection of oestradiol benzoate not only made ovariectomized rats receptive, but also made their preputial gland odours attractive to male rats. The results suggest that the preputial gland of the female rat is responsible for odours that serve to attract sexually experienced male rats. Ovarian steroids, as well as controlling receptivity in the female rat, would also appear to control the production of sex attractants in the preputial gland. There was no relationship between the size of the preputial glands and their ability to attract male rats which suggests that preputial gland growth and production of sex attractants are not under the same hormonal control.

INDUCTION OF SEXUAL RECEPTIVITY IN OVARIECTOMIZED RATS BY PULSE ADMINISTRATION OF OESTRADIOL-17β

1981 ◽  
Vol 89 (1) ◽  
pp. 55-62 ◽  
Author(s):  
P. SÖDERSTEN ◽  
P. ENEROTH ◽  
S. HANSEN
Keyword(s):  
Single Injection ◽  
Serum Levels ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Sexual Receptivity ◽  
Behavioural Responses ◽  
Time Points ◽  
Progesterone Treatment ◽  
Oestradiol Benzoate ◽  
Stimulation Of

Constant-release implants filled with oestradiol-17β induced sexual receptivity in ovariectomized rats in response to progesterone treatment if they were implanted 32 h before behavioural testing. A 20 h period of exposure to oestradiol, by implantation 32 h before testing and removal of the implants 20 h later, was sufficient for induction of the behaviour. The exposure time necessary for behavioural responses could be further reduced to two 4 h periods, between 32 and 28 h and between 16 and 12 h, before testing. Serum levels of oestradiol were raised within 1 h of oestradiol implantation and declined rapidly after implant removal. A single injection of oestradiol benzoate was much more potent than a single injection of oestradiol in inducing sexual receptivity in ovariectomized rats, but this difference in potency was reversed if two appropriately timed injections were given. Oestrone- or oestriol-filled implants were relatively ineffective in inducing sexual receptivity. It is suggested that oestradiol has to be present at crucial time points to prepare an ovariectomized rat to respond behaviourally to progesterone treatment and that oestradiol is the principal oestrogen in the stimulation of sexual behaviour in female rats.

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.

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