Agonistic activity of tamoxifen, a selective estrogen-receptor modulator (SERM), on arthritic ovariectomized mice

Arthritis is positively associated with the decline of sex hormones, especially estrogen. Tamoxifen (TMX) is a selective estrogen receptor modulator, possessing agonist or antagonistic activity in different tissues. Thus, the objective of this study was to investigate the effect of TMX on the zymosan-induced arthritis model. Female Swiss normal and ovariectomized (OVX) mice were divided into groups and treated for five days with TMX (0.3, 0.9 or 2.7 mg/kg) or 17-β-estradiol (E2, 50 µg/kg). On the fifth day, arthritis was induced and 4 h later, leukocyte migration into joint cavities was evaluated. The neutrophil migration in OVX animals, but not in normal mice, treated with TMX (all tested doses) was significantly decreased compared with mice that received the vehicle (P≤0.05). Similarly, this effect was also demonstrated in the E2-treated group. Therefore, the present study demonstrates that TMX presented agonist effects in inhibiting neutrophil migration and preventing arthritis progression in OVX mice.

Efecto del 27- hidroxicolesterol en la acción antiplaquetaria de estradiol en mujeres postmenopáusicas / 27- Hydroxycholesterol reverses estradiol induced inhibition of platelet aggregation in postmenopausal women

Background: The decline of estrogen levels increases cardiovascular risk in women. Platelets express estrogen receptors and 17β-estradiol- (E2) can produce a protective effect on thrombus formation. The hydroxylation of cholesterol generates several sterols and 27-hydroxycholesterol (27HC) predominates in circulation. Aim: To evaluate the effect of 27HC as an endogenous antagonist of the anti-aggregating properties of E2 in platelets of postmenopausal women. Material and Methods: Platelet function of postmenopausal women was evaluated ex-vivo. Platelets pre-incubated with 27HC in the presence or absence of E2, were stimulated with collagen. Aggregation was evaluated using turbidimetry using a Chrono-log aggregometer. Results: Collagen-stimulated platelet aggregation was significantly inhibited by E2. The inhibitory effect of E2 on collagen-stimulated platelet aggregation was significantly reversed in the presence of 27HC. Conclusions: The suppressive effect of E2 on platelet aggregation is inhibited by 27HC, which could contribute to increase cardiovascular risk in postmenopausal women.

Boys in white: um clássico da pesquisa qualitativa completa cinquenta anos / Boys in white: a classic of qualitative research turns 50

O artigo analisa o livro Boys in white: student culture in medical school, de Howard S. Becker, Blanche Geer, Everett C. Hughes e Anselm Strauss, considerado um dos modelos de pesquisa qualitativa em sociologia. A análise aborda as trajetórias dos autores, do livro, da pesquisa qualitativa e dos estudantes de medicina, enfatizando sua importância nas origens da sociologia médica e da sociologia da educação médica. Na trajetória dos autores são apresentados aspectos biobibliográficos; na da pesquisa qualitativa, o modo como essa metodologia de investigação atravessa a construção do trabalho de campo; e na dos estudantes, sua forma de atravessar os primeiros anos da escola médica e construir sua própria “cultura do estudante”.

This article analyzes Boys in white: student culture in medical schoolby Howard S. Becker, Blanche Geer, Everett C. Hughes and Anselm Strauss, considered a model of qualitative research in sociology. The analysis investigates the trajectories of the authors, the book, qualitative analysis, and the medical students, emphasizing their importance in the origins of medical sociology and the sociology of medical education. In the trajectory of the authors, bibliographical information is given. The trajectory of qualitative research focuses on how this methodology influences the construction of the field. The investigation of the students’ trajectory shows how they progress through their first years at medical school to build their own student culture.

Stereological Comparison of the Effects of Pentoxifylline, Captopril, Simvastatin, and Tamoxifen on Kidney and Bladder Structure After Partial Urethral Obstruction in Rats

PURPOSE: Limited studies have shown antifibrotic effects of pentoxifylline, captopril, simvastatin, and tamoxifen. No comparisons are available of the effects of these drugs on prevention of renal and bladder changes in partial urethral obstruction (PUO). MATERIALS AND METHODS: The rats were divided into six groups (n=7). The sham-operated rats (group I) only underwent laparotomy and did not receive any treatments. The PUO groups (group II-VI) received normal saline (PUO+NS), pentoxifylline (100 mg/kg/d; PUO+PEN), captopril (35 mg/kg/d; PUO+CAP), simvastatin (15 mg/kg/d; PUO+SIM), or tamoxifen (10 mg/kg/d; PUO+TAM) by gavage for 28 days. Then, the volume and/or length of the kidney components (tubules, vessels, and fibrous tissue) and the bladder components (epithelial and muscular layers, fibrous tissue, fibroblast and fibrocyte number) were quantitatively evaluated on the microscopic sections by use of stereological techniques. RESULTS: The volume of renal and bladder fibrosis was significantly ameliorated in the PUO+PEN group, followed by the PUO+CAP, PUO+SIM, and PUO+TAM groups. Also, the volume and length of the renal tubules and vessels and bladder layers were more significantly protected in the PUO+PEN group, followed by the PUO+CAP, PUO+SIM, and PUO+TAM groups. CONCLUSIONS: Treatment of PUO with PEN was more effective in the prevention of renal and bladder fibrosis and in the preservation of renal and bladder structures.

Estradiol regulates miR-135b and mismatch repair gene expressions via estrogen receptor-beta in colorectal cells

Estrogen has anti-colorectal cancer effects which are thought to be mediated by mismatch repair gene (MMR) activity. Estrogen receptor (ER) expression is associated with microRNA (miRNA) expression in ER-positive tumors. However, studies of direct link between estrogen (especially estradiol E2), miRNA expression, and MMR in colorectal cancer (CRC) have not been done. In this study, we first evaluated the effects of estradiol (E2) and its antagonist ICI182,780 on the expression of miRNAs (miR-31, miR-155 and miR-135b) using COLO205, SW480 and MCF-7 cell lines, followed by examining the association of tissue miRNA expression and serum E2 levels using samples collected from 18 colorectal cancer patients. E2 inhibited the expressions of miRNAs in COLO205 cells, which could be reversed by E2 antagonist ICI 182.780. The expression of miR-135b was inversely correlated with serum E2 level and ER-beta mRNA expression in CRC patients' cancer tissues. There were significant correlations between serum E2 level and expression of ER-beta, miR-135b, and MMR in colon cancer tissue. This study suggests that the effects of estrogen on MMR function may be related to regulating miRNA expression via ER-beta, which may be the basis for the anti-cancer effect in colorectal cells.

Contraceptive, estrogenic and anti-estrogenic potentials of methanolic root extract of carpolobia lutea a in rodents

Several plants are used in herbal medicine for family planning. Carpolobia lutea is a medicinal plant in South Eastern Nigeria used for family planning. The study, was designed to investigate the contraceptive, estrogenic and antiestrogenic potentials of the methanolic root extract of Carpolobia lutea in both rats and mice. The contraceptive effect of extract [7 - 21mg/kg] administered by intraperitoneal route for four days in divided doses was tested in mice and rats. Sexually-active males were introduced on day 5 at the ratio of 3F:1M and kept with these females till the end of the experiment. Investigations on the estrogenic and antiestrogenic property of the extract [7-21mg/kg] were done in immature rats that had undergone surgical removal of both ovaries. The effects of the extract [vaginal opening, vaginal cornification, uterine wet weight] were compared with 17-beta-estradiol [0.l micro g/rat/day] as standard drug. Twenty-four hours later, the animals were sacrificed following the last dose and the weights of uterus, kidney, liver and small intestine were recorded. The extract prevented conception in both mice and rats for two gestational periods. Significant changes [p<0.05-0.001] were observed in the length and weight of pups relative to control. There were no abnormalities observed in the pups over thirty days. In ovariectomized immature young rats, the extract showed estrogenic effect [vaginal opening, vaginal cornification and increased uterine wet weight] in low doses while in high doses, it showed antiestrogenic effect. These findings agree with the traditional use of Carpolobia lutea in the control of fertility. The contraceptive property of the extract may be associated with the direct effects of its chemical constituents

Chronic treatment with the nitric oxide synthase inhibitor, L-NAME, attenuates estradiol-mediated improvement of learning and memory in ovariectomized rats

INTRODUCTION: The role of ovarian hormones and nitric oxide in learning and memory has been widely investigated. OBJECTIVE: The present study was carried out to evaluate the effect of the nitric oxide synthase (NOS) inhibitor, N (G)-nitro-L-arginine methyl ester (L-NAME), on the ability of estradiol to improve learning in OVX rats using the Morris water maze. METHODS: Forty rats were divided into five groups: (1) ovariectomized (OVX), (2) ovariectomized-estradiol (OVX-Est), (3) ovariectomized-L-NAME 10 (OVX-LN 10), (4) ovariectomized-L-NAME 50 (OVX-LN 50) and (5) ovariectomized-estradiol-L-NAME 50 (OVX-Est-LN 50). The animals in the OVX-Est group were treated with a weekly injection of estradiol valerate (2 mg/kg; i.m.). The OVX-LN 10 and OVX-LN 50 groups were treated with daily injections of 10 and 50 mg/kg L-NAME (i.p.), respectively. The animals in the OVX-Est-LN 50 group received a weekly injection of estradiol valerate and a daily injection of 50 mg/kg L-NAME. After 8 weeks, all animals were tested in the Morris water maze. RESULTS: The animals in the OVX-Est group had a significantly lower latency in the maze than the OVX group (p<0.001). There was no significant difference in latency between the OVX-LN 10 and OVX-LN 50 groups in comparison with the OVX group. The latency in the OVX-Est-LN 50 group was significantly higher than that in the OVX-Est group (p<0.001). CONCLUSION: These results show that L-NAME treatment attenuated estradiol-mediated enhancement of spatial learning and memory in OVX rats, but it had no significant effect in OVX rats without estrogen, suggesting an interaction of nitric oxide and estradiol in these specific brain functions.

Influence of estradiol and triiodothyronine on breast cancer cell lines proliferation and expression of estrogen and thyroid hormone receptors / Efeito do estradiol e da triiodotironina na proliferação de linhagens celulares de câncer de mama e na expressão de receptores de estrógeno e hormônio tireoidiano

OBJECTIVE: To better understand the estrogen (E2) agonist action of triiodothyronine (T3) the effects of these hormones on ER negative MDA-MB-231 breast cancer cells were compared with those on S30, a clone of MDA-MB-231 stably transfected with ERα cDNA, in terms of proliferation and modulation of hormone receptors. RESULTS: Growth experiments showed that MDA-MB-231 was not modulated by any hormone or tamoxifen (TAM). Treatment with E2, 10-8M or 10-9M had little effect on S30 proliferation. T3 at 10-8M significantly inhibited proliferation. This effect was not reverted by TAM. Treatments with 10-8M concentration of E2 or T3 reduced ERα gene expression in S30, an effect partially blocked by association with TAM, with no effect on TR expression. These results suggest that, in S30, 10-8M T3 has a similar action to E2 relative to ERα gene modulation. CONCLUSIONS: Such results emphasize the need of determining T3 levels, before the introduction of antiestrogenic forms of treatment in breast cancer patients.

OBJETIVO: Para compreender melhor a ação da triiodotironina (T3) agonista de estrógeno (E2), foram comparados os efeitos destes hormônios em células de câncer de mama MDA-MB-231 ER negativas com um clone de MDA-MB-231, transfectado estavelmente com o cDNA de ERα (S30), em termos de proliferação e modulação dos receptores hormonais. RESULTADOS: Experimentos de crescimento mostraram que MDA-MB-231 não foi modulada por qualquer hormônio ou pelo tamoxifeno (TAM). O crescimento de S30 foi essencialmente inalterado por tratamento com E2 10-9M ou 10-8M, mas T3 10-8M inibiu significativamente a proliferação quando comparada a ambas concentrações de E2. Esse efeito não foi revertido pelo TAM, sugerindo um resultado não genômico, independente de ERE. Tratamentos com 10-8M de E2 ou de T3 reduziram a expressão do gene ERα em S30, efeito parcialmente impedido pela associação com TAM, sem efeito na expressão de TR. Os resultados sugerem que, em S30, T3 10-8M tem ação semelhante ao E2 com relação à modulação do gene ERα. CONCLUSÕES: Esses resultados enfatizam a necessidade de dosagem de T3 circulante antes da introdução do tratamento antiestrogênico no câncer de mama.

Compuestos disruptores endocrinos y su participación en la programación del eje reproductivo / Endocrine disruptor compounds and their role on the developmental programming of the reproductive axis

Different perturbations during fetal and post natal development unleash endocrine adaptations that permanently alter metabolism, increasing the susceptibility to develop later disease, process known as "developmental programming"'. Endocrine disruptor compounds (EDC) are widely spread on the environment and display estrogenic, anti-estrogenic or anti-androgenic activity; they are lypophilyc and stored for long periods on the adipose tissue. Maternal exposure to EDC during pregnancy and lactation produces the exposure of the fetus and neonate through placenta and breast milk. Epidemiological and experimental studies have demonstrated reproductive alterations as a consequence of intrauterine and/or neonatal exposure to EDC. Diethystilbestrol (DES) is the best documented compound, this synthetic estrogen was administered to pregnant women at the BO and 60 to prevent miscarriage. It was implicated in urogenital abnormalities in children exposed in utero and withdrawn from the market. The "DES daughters" are women with high incidence of vaginal hypoplasia, spontaneous abortion, premature delivery, uterine malformation, menstrual abnormalities and low fertility. The "DES sons" show testicular dysgenesis syndrome, which is characterized by hypospadias, cryptorchidism and low semen quality. This entity is also associated to the fetal exposure to anti-androgens as flutamide. The effects on the reproductive axis depend on the stage of development and the window of exposure, as well as the dose and the compound. The wide distribution of EDC into the environment affects both human health and ecosystems in general, the study of their mechanisms of action is extremely important currently.

Diversas perturbaciones durante el desarrollo fetal y posnatal desencadenan adaptaciones endocrinas que modifican permanentemente el metabolismo, incrementando la susceptibilidad para el desarrollo de enfermedades, proceso conocido como "programación durante el desarrollo". Los compuestos disruptores endocrinos (CDE) se encuentran en el medio ambiente y presentan actividad estrogénica, antiestrogénica o antiandrogénica; son altamente lipofílicos y se almacenan por periodos prolongados en el tejido adiposo. La exposición materna a CDE durante el embarazo y la lactancia permite su paso al producto a través de la placenta y la leche materna. Estudios epidemiológicos y experimentales han demostrado alteraciones en el eje reproductivo como consecuencia de la exposición intrauterina y/o neonatal a CDE. El compuesto mejor documentado es el dietilestilbestrol (DES), este estrógeno sintético fue administrado a mujeres embarazadas durante los 50s y 60s y retirado del mercado por su implicación en anormalidades urogenitales de los bebés expuestos in útero. Las denominadas "hijas del DES" son mujeres con alta incidencia de hipoplasia vaginal, malformaciones uterinas, irregularidades menstruales, baja fertilidad y alta prevalencia de aborto espontáneo y parto prematuro. Por su parte, "los hijos del DES" presentan una entidad clínica conocida como síndrome de disgenesia testicular caracterizado por hipospadias, criptorquidia y baja calidad del semen. Este síndrome también se asocia a la exposición fetal a compuestos antiandrogénicos como la ñutamida. Los efectos en el eje reproductivo dependen del estadio de desarrollo y del tiempo de exposición, así como de la dosis y el compuesto del que se trate. La extensa presencia de CDE en el ambiente afecta la salud humana e impacta al ecosistema en general por lo cual es de suma importancia el estudio de los mecanismos involucrados en su acción.

Effect of conjugated equine estrogens and tamoxifen administration on thyroid gland histomorphology of the rat

OBJETIVO: Avaliar a ação dos estrogênios conjugados eqüinos e do tamoxifeno na histomorfologia da tireóide de ratas. MÉTODO: Estrogênios conjugados eqüinos são ministrados clinicamente como terapia estrogênica e contêm formulação complexa com muitos tipos de estrogênios que diminuem os sintomas da pós-menopausa. Trinta ratas adultas ooforectomizadas foram divididas aleatoriamente em três grupos: GI – veículo (propilenoglicol); GII - ECE 200 µg/Kg por dia; e GIII – TAM 1 mg/Kg por dia. Acrescentou-se ainda um grupo de 10 animais com os ovários intactos e tratados com veículo (GIV). Todos os animais foram tratados por gavagem durante 50 dias consecutivos, ao final foram coletadas amostras do sangue e a tireóide removida e processada para análise morfológica e imunohistoquímico para avaliar o PCNA. RESULTADOS: A maior altura das células foliculares foi observada nos animais tratados com ECE (14,90 ± 0,20 µm), TAM (14,90 ± 0,10 µm) e no grupo com ovários intactos (15,10 ± 0,50 µm), comparando-se aos controles ovariectomizados (GI) (9,90 ± 0,20 µm) (p<0,001). A maior área folicular foi detectada nos grupos tratados com ECE (2.225 ± 51 µm2) e com TAM (2.127 ± 67 µm2), comparado ao veículo (5.016 ± 53 µm2) em animais ooforectomizados. Os níveis de T4 e T3 nos grupos tratados com ECE, com TAM e no grupo com ovários intactos foram maiores do que no grupo tratado com veículo (p<0,001). O índice do PCNA no grupo tratado com veículo foi menor do que em todos os outros grupos. CONCLUSÃO: Nossos dados sugerem que a administração de ECE e TAM resulta em atividade proliferativa na tireóide.

Efeito do tamoxifeno no perfil das proteínas plasmáticas em condição de diabetes mellitus tipo 1 / Effect of tamoxifen on plasma proteins in diabetes mellitus type 1

OBJETIVO: Considerando-se que importantes avanços científicos têm sido obtidos através de estudos com Diabetes mellitus experimental, e que a ação do tamoxifeno em humanos permanece obscura, o presente trabalho objetiva acompanhar as modificações promovidas pelo diabetes e tamoxifeno no perfil eletroforético das proteínas plasmáticas. MÉTODOS: Foram utilizados 27 ratos fêmeas Wistar (180-220g peso corporal), divididos randomicamente em 5 grupos: C1 (n=3, receberam veículo), C2 (n=3, sem tratamento), T (n=5, tratados com tamoxifeno, 0,3mg/kg/dia), D (n=8, diabéticos experimentais por estreptozotocina, 45mg/Kg) e DT (n=8, diabéticos tratados com tamoxifeno). A eletroforese foi realizada em acetato de celulose, pH 8,6-8,8, cuba TECNOW, e as fitas foram coradas em Ponceau S. As proteínas totais foram determinadas pelo método do Biureto (Kit Labtest). Os proteinogramas foram obtidos em densitômetro BioSystems BTS-235. RESULTADOS: Albumina diminuiu progressivamente nos grupos T, D e DT; a fração a1 aumentou nos grupos T e DT; a fração a2 aumentou nos grupos T e D, havendo efeito aditivo no grupo DT; a fração b aumentou nos grupos T e D; a fração g aumentou nos grupos T, D e DT. CONCLUSÃO: Os resultados indicam uma resposta de fase aguda, com efeito aditivo do tamoxifeno e diabetes, sugerindo uma provável lesão hepática.

Expression of adenosine deaminase and 5'-nucleotidase in artificially induced deciduoma in rat and hamster.

Enzymes adenosine deaminase (ADA) and 5-nucleotidase (5-'NT) are known to play active role in tissue/cell proliferation and differentiation. To validate this the two enzymes were studied in artificially induced deciduoma of rat and hamster. The deciduoma was induced by traumatizing one of the uterine horns of progesterone primed animals. Non traumatized horn served as control. The animals were later maintained on progesterone, given alone (Gr.I) or conjointly with estrogen (Gr.II). The weight of each uterine horn was recorded to determine the formation of deciduoma. There was no marked difference between the weights of traumatized and control horn on day 2 post-traumatization (PT), but a progressive rise was noticed after this day in both species. The ADA activity however differed, day and species wise. While in the rats of Gr.I it was low in the traumatized horn on all the days, in the hamsters it was remarkably high from day 2 to 6 PT. In the rats of Gr.II also the activity though was low in the traumatized horn, but on day 2 and 4 only; on day 6 and 7 PT it increased markedly. In hamster, on the contrary, again the enzyme activity was remarkably high on all the three days. The 5'-NT activity, however, did not show any marked difference between the two horns under Gr.I and II in both species. It was rather high in the control horn of each group. The results suggest: (I) the progesterone alone though produces a significant rise in the uterine weight of traumatized horn in both species, the ADA activity increases only in hamster, (2) under the conjoint treatment also the enzyme activity remains high in hamster; and (3) the activity of enzyme 5'-NT does not alter during the deciduoma formation in both the species.

Identification of a mutation in the human raloxifene response element of the transforming growth factor-3 gene

The human transforming growth factor-3 (TGF-3) is an important cytokine to maintain bone mass by inhibiting osteoclast differentiation. Recently raloxifene response element (RRE), a new enhancer with a polypurine sequence for estrogen receptor (ER)-mediated gene activation, was identified on the TGF-3 gene. Functional analysis of the RRE-mediated pathway has shown that this would be an important pathway for bone preserving effect. We found a novel mutation in the RRE sequence by single-strand conformational polymorphism analysis in one of 200 Korean women. Cloning and sequencing revealed a heterozygote in which one allele had an insertion of 20 nucleotides (AGAGAGGGAGAGGGAGA GGG) between nucleotide +71 and +72 and a point mutation at nucleotide +75 (G-A transition), and the other allele had normal sequence. The insertion was a nearly perfect tandem duplication of the wild type DNA sequence. The bone mineral density of the affected woman was not much lower than that of age-matched controls. Transient transfection of the mutant allele showed no significantly different activity compared with that of the wild type allele. These observations suggest that the heterozygote variation of the RRE sequence seems not to be operative in determination of bone mass.

Effect of CDRI-85/287, a potent antiimplantation agent on uterine endometrial dimensions and peroxidase levels in rat.

CDRI compound 85/287 a potent estrogen antagonist and antiimplantation agent in rat was studied to elucidate its mechanism of action. In ovariectomized rats 85/287 treatment antagonized estrogen stimulated uterine volume density, eosinophil leucocyte infiltration, stromal mitotic cell number and peroxidase activity. In parallel experiments in pregnant rats, uterine peroxidase activity also decreased significantly as compared to controls on day 5 post-coitum. The results show that 85/287 exerts its antiimplantation activity by inhibition of responses to estradiol action.

Danazol-induced biochemical changes in the rat ovary.

Effect of varying doses of danazol, a synthetic steroid derivative of 17 alpha-ethinyl testosterone has been observed on the biochemistry of the rat ovary. Biochemically total proteins decreased and total lipids increased with the danazol treatment. Triglycerides, the stored form of lipids formed the major components of lipids in the treated ovaries. The amount of phospholipids, glycolipids, cholesterol and free fatty acids decreased in the ovaries with increased danazol treatment. The functional significance of these changes have been discussed with ovarian physiology especially in relation to follicular growth and atresia.

Papel do raloxifeno, um modulador seletivo de receptor estrogênico, na manutençäo da saúde da mulher na pós menopausa / Role of raloxifene, a selective estrogen receptor modulator, in the health maintenance of postmenopausal women

Estudos pré clínicos em modelos animais e estudos clínicos em mulheres na pós menopausa demonstram que o raloxifeno tem um perfil farmacológico único relativo aos estrogênios e outros compostos com açäo estrogênica descritos até agora. As açöes seletivas agonistas nos sistemas esqueléticos e cardiovasculares, as açöes antagonistas nos tecidos uterino e mamário, combinados com tolerabilidade e aceitabilidade, fazem do raloxifeno um agente de prevençäo e potencialmente de tratamento para a osteoporose da pós menopausa.

In-vitro effect of estrogen-antagonist on motility and penetration ability of human spermatozoa.

Antiestrogens affect spermatozoa through their action on Leydig and Sertoli cells. Direct effect of antiestrogens namely tamoxifen and centchroman in concentration of 1, 2.5, 5, 10 and 20 micrograms/ml in incubation medium was determined on motility and penetration ability of human spermatozoa. Motility (%) was invariably reduced after 15, 30 and 60 min. of incubation. Addition of 17 beta-estradiol to medium with antagonist caused inhibition of motility in dose related manner. The distance travelled by spermatozoa treated with tamoxifen or centchroman in media was reduced by 30% and addition of estradiol along with antiestrogen reduced it to 50% compared to that of untreated spermatozoa.

Study of the action of tamoxifen on the mammary gland epithelium of premenopausal patients by lysosome quantification

Tamoxifen is an antiestrogen drug widely utilized for the adjuvant hormonal treatment of breast carcinoma. Its use in the primary prophylaxis of this disease is currently being proposed. Although the drug has few side effects, its precise action on breast tissue that has not undergone neoplastic transformation has not been fully elucidated. This prospective, randomized study assessed the estrogen activity of tamoxifen on the mammary gland epithelium of premenopausal patients using a quantitative analysis of mammary epithelium lysosomes identified by the cytochemical technique of GOMORI for acid phosphatase and by light microscopy. Tamoxifen significantly increased the number of lysosomes only during the secretory phase of the menstrual cycle. We concluded that the early effect of the drug on normal mammary tissue is synergistic with the effect of estrogen during the premenopausal period.

Response of the postnatal rat epididymis to estrogen & antiestrogens.

The effect of androgen and estrogen antagonists on estrogen induced responses in the epididymis of rat was studied. Estradiol benzoate administered to male rates on day 5 of life increased the epididymal weight, absolute volume density of fibromuscular stroma and its eosinophilic leucocyte numbers. Testosterone administration (day 5 life) alone did not have any stimulatory effect on the epididymis as an organ or its peroxidase activity on days 15 or 20 of life. On the other hand, testosterone/85/287 negated estradiol induced increase in the absolute volume density, eosinophilic leucocyte accumulation and peroxidase activity. Tamoxifen (Tam) with inherent estrogenic activity acted both as an agonist and an antagonist. Results of present studies support the contention that nonsteroidal antiestrogens (CDRI-85/287 and Tam) can modulate estradiol induced epididymal responses during the postnatal period of male rat.