Progestin Receptor Concentrations Research Articles

The ontogeny of cytosol and nuclear progestin receptors in male rat brain and its male-female differences

The fetal and postnatal development of the progestin receptor systems in the intact male rat brain was investigated by means of the in vitro cytosol binding and the nuclear exchange assay using [ 3H]R5020 ([17α-methyl- 3H]17α,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione). The cortical cytosol receptors, first detectable at day 0, rapidly increased at day 7, reaching a maximum at day 10, then gradually declined thereafter. The receptors in the HPOA appeared clearly at day 1, increased during the first 10 days, then remained constant at days 14–21. The postnatal developmental patterns of cytosol brain progestin receptors in males were essentially similar to those in females, but there were some differences between both sexes. The male HPOA at days 10–14 contained more receptors than the female one. Nuclear progestin binding was low in the neonatal male brain at days 1–3. Despite the low level of serum progesterone, the cortical nuclear binding suddenly increased at days 7–10, then remained high at days 14–21. A similar, though less pronounced, pattern was seen in the HPOA. The male pattern of nuclear binding, thus, essentially resembled the female one. However, lower binding in the cortex and, possibly, HPOA was found in males than in females at days 10–21. After progesterone injection postnatal male rats accumulated a lower concentration of progestin receptors in the cortex and, possibly, HPOA than similarly-treated females. It is concluded from these results that progestin receptors in male rat brain appear immediately after birth and develop differentially in the cortex and HPOA. The sudden onset of increased nuclear translocation of endogenous progestin receptor complexes may occur in the brain at around days 7–10. There is a marked sex difference in the nuclear progestin receptor system in the postnatal brain, particularly the cortex. Moreover, the postnatal male brain has lower capacities of nuclear receptor translocation than does the female one. The progestin receptor system in the cortex and, possibly, HPOA of rats in the early postnatal life might be involved with some processes in the mechanism of sexual differentiation of the brain.

Supplemental progesterone delays heat termination and the loss of progestin receptors from hypothalamic cell nuclei in female guinea pigs.

Previous studies indicate that the retention of hypothalamic nuclear progestin receptors parallels the expression of sexual receptivity in ovariectomized, hormonally treated guinea pigs. In this study, the effect of a supplemental progesterone injection on heat termination and retention of nuclear progestin receptors was examined. Ovariectomized guinea pigs were injected with 50 micrograms progesterone 48 h after receiving 4 micrograms estradiol benzoate and were tested hourly for lordosis. 8 h after progesterone treatment, animals received either 500 micrograms progesterone or the oil vehicle. The supplemental progesterone injection delayed the termination of heat by more than 2 h compared to oil-injected animals. The effect of supplemental progesterone on the retention of nuclear progestin receptors was then determined. Animals were killed 8, 10, or 14 h after the initial injection of progesterone, and cytosol and nuclear progestin receptor concentrations in mediobasal hypothalamus-preoptic area were determined. Supplemental progesterone further increased the level of nuclear progestin receptors measured at 10 h, and at 14 h these levels were still elevated above baseline. In contrast, nuclear progestin receptor levels in animals which received only the initial progesterone injection had returned to baseline by 14 h, a time when similarly treated animals were no longer receptive. These results suggest that the mechanism by which heat termination occurs may involve loss of nuclear progestin receptors.

Estrogen agonistic and antagonistic action of 8 non-steroidal antiestrogens on progestin receptor induction in rat pituitary gland and uterus

All 8 non-steroidal antiestrogens tested considerably increased progestin receptor concentration in the uterus and, to a lesser extent, in the pituitary of ovariectomized rats. However, the pituitary was more sensitive than the uterus to the estrogen antagonistic action of these compound, in that monohydroxytamoxifen, LY 117, 018, enclomiphene, nitromifen, nafoxidine and trans-tamoxifen completely blocked progestin receptor induction by estradiol benzoate. In these tissues the order of the in vitro binding affinity of antiestrogens to cytoplasmic estrogen receptors was not correlated with either their in vivo estrogen agonistic or antagonistic potency.

Cytoplasmic progesterone receptors in the hypothalamus-preoptic area of the mouse: Effect of estrogen priming

A synthetic progestin, R5020, was used to identify cytoplasmic progestin receptors in the hypothalamuspreoptic area (HPOA) of ovariectomized mice. These high-affinity receptors exhibited an apparent dissociation constant of approx. 1 nM. The receptors were specific for progestins. [ 3H]R5020 binding was inhibited by more than 50% with a 50-fold excess of either radioinert R5020 or progesterone. 5α-Dihydroprogesterone inhibited binding to a lesser extent. 3α-Hydroxy-5α-pregnane 20-one and cortisol did not compete for [ 3H]R5020 binding. Administration of estradiol benzoate (10 μg), 48 h prior to death, resulted in a 54% increase in the HPOA progestin receptor concentration when compared to oil-injected controls. These data demonstrate that there are specific and saturable cytoplasmic progestin receptors in the mouse HPOA and that the concentration of these receptors is increased after estrogen treatment.

Cytosol and nuclear estrogen and progestin receptors and 17 beta‐hydroxysteroid dehydrogenase activity in non‐diseased tissue and in benign and malignant tumors of the human ovary

Significant but low concentrations (mean 8 fmol/mg cytosol protein) of cytosol estrogen receptors were found in 57% of non-diseased ovarian tissues, and higher concentrations (mean 211) of cytosol progestin receptors in all these tissues. An approximately similar distribution was found for the presence of nuclear female sex steroid receptors; the mean concentrations were 159 and 1149 sites/cell, for estrogen and progestin receptors, respectively. There were no major differences in these parameters between pre- and postmenopausal non-diseased ovaries. The activities of ovarian 17 beta-hydroxysteroid dehydrogenase (17-HSD) did not display correlations between circulating progesterone concentrations in pre- or postmenopausal women with non-diseased ovaries. The majority of benign epithelial tumors contained significant concentrations of cytosol estrogen receptors, and all showed cytosol progestin receptors. The concentration of estrogen receptors was identical to that seen in non-diseased ovaries (mean 9 fmol/mg cytosol protein), whereas that of progestin receptor was significantly lower (mean 95). Nuclear female sex steroid receptors were measured in all benign tumors, and their concentrations were significantly higher than in normal ovaries (440 and 3218 sites/cell for estrogen and progestin receptors, respectively). No difference in 17-HSD activities were detected between normal ovaries and benign tumors. In malignant ovarian tumors, the picture was different from that found in normal ovarian tissues and benign tumors. Cytosol estrogen receptor was found in 89% of malignant epithelial tumors, and its concentration was significantly higher (mean 64 fmol/mg cytosol protein). Cytosol progestin receptor was found in 91%, and its concentration (mean 75) was significantly lower than in normal ovarian tissue or benign ovarian tumors. Nuclear female sex steroid receptor concentrations were intermediate between those seen in non-diseased ovaries an in benign tumors. 17-HSD activity was significantly lower than in other tissue categories studied. In the small group (16) of non-epithelial ovarian carcinomas cytosol estrogen receptors were not found, whereas the results of other measurements did not display any coherent picture. Breast and endometrial carcinoma metastatic to the ovary showed receptor patterns which were typical of the primary tumors. When the different clinical stages (I-IV) of malignant epithelial ovarian tumors were compared, 17-HSD activity was significantly higher in the least advanced clinical stage (I), whereas no significant differences were found in the other parameters measured.(ABSTRACT TRUNCATED AT 400 WORDS)

Progestin-like effects of danazol on rabbit uterus.

The action of danazol on cytosol and nuclear progestin and estrogen receptor concentrations and on the induction of uteroglobin synthesis were studied in the rabbit uterus in vivo. In addition, the relative binding affinity of danazol for the uterine progestin receptor was measured in vitro. Administration of increasing doses of danazol (10, 50, or 100 mg/kg BW daily) for 5 days to adult rabbits tended to decrease the concentrations of cytosol and nuclear progestin and estrogen receptors, whereas the uterine uteroglobin content increased with increasing doses of danazol. Progesterone (1 mg/kg BW daily) caused changes which were greater than those caused by the largest dose of danazol. Danazol was found to bind to the uterine progestin receptor in vitro with an affinity approximately 3.3% of that of progesterone. These findings suggest that danazol has a profound progestin-like activity in the rabbit uterus which may be mediated through binding to cytosol progestin receptors.

Estrogen receptors and estrogen-inducible progestin receptors in the sexual skin of the monkey

Estrogen-binding macromolecules were identified in sexual skin cytosol and nuclear fractions from female Japanese monkeys ( Macaca fuscata fuscata), by sucrose-glycerol gradient analysis and dextrancoated charcoal adsorption technique. Furthermore, using the highly potent synthetic progestin, R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione; promegestone), progestin-binding macromolecules were detected in sexual skin cytosols from ovariectomized estrogen-primed monkeys. Both cytosol components sedimented at the 8S region on sucrose-glycerol gradients and had a highaffinity for the respective steroids, and competition studies showed a specificity for estrogenic, or progestational compounds. The concentration of cytosol progestin receptors was markedly increased with the elevated level of nuclear estrogen receptors following estrogen priming. The above results demonstrate the existence of cytosol and nuclear estrogen receptor sites, and estrogen-induced progestin receptors in the sexual skin of the female monkeys.

Changes in concentration of hypothalamic cytosolic progestin receptors at the initiation of pseudopregnancy in rats.

Pseudopregnancy (psp) can be induced by a single injection of progesterone in cyclic rats and the administration of anti-progesterone serum can block the establishment of psp in cervically stimulated rats. To further investigate neuroendocrine mechanisms for the initiation of either psp or prolactin (PRL) surges in connection with the neurotropic action of progesterone, cytosolic progestin receptors (PRc) were identified and measured in preoptic (POA) and basal hypothalamic (BH) areas. Chronological determinations of PRc concentrations in both areas revealed large fluctuations in the morning of the estrous day but not in the morning of the diestrous day. The differences between the maximal and the minimal PRc concentrations observed were more than 100-fold in POA and 3-fold in BH. Cervical stimulation applied in the afternoon of the proestrous day significantly altered the changing pattern of PRc concentrations in POA but not in BH. One of the two peaks of PRc concentrations in POA was magnified and advanced earlier to 0300 h, and then the 1st PRL surge peaking at 0700 h occurred. This PRL release seemed to stimulate progesterone secretion and an elevation of peripheral progesterone levels coincided with the 2nd peak of PRc concentrations in POA at 0900 h. This coincidence may be a prerequisite for the further continuation of PRL surges. These results strongly suggest that the spontaneous oscillation of the PRc concentration in hypothalamic neurons is involved in the regulation of PRL secretion and that cervical stimulation shifts the phase and changes the amplitude.

Neurotransmitter-controlled steroid hormone receptors in the central nervous system

Results are discussed indicating that neurotransmitters affect steroid hormone activity not only by controlling via neuroendocrine events the hypophysial-gonadal and hypophysial-adrenal axes, but also by modulating cell responsiveness to steroids in target cells. Hyper- or hypoactivity of pineal nerves result in enhancement or impairment of estradiol and testosterone effects on pineal metabolism in vivo and in vitro. Pineal cytoplasmic and nuclear estrogen and androgen receptors are modulated by norepinephrine released from nerve endings at the pinealocyte level. Neural activity affects the cycle of depletion-replenishment of pineal estrogen receptors following estradiol administration. Another site of modulation of steroid effects on the pinealocytes is the intracellular metabolism of testosterone and progesterone; nerve activity has a positive effect on testosterone aromatization and a negative effect on testosterone and progesterone 5?-reduction. NE activity on the pineal cells is mediated via ?-adrenoceptors and cAMP. In the central nervous system information on the neurotransmitter modulation of steroid hormone action includes the following observations: (a) hypothalamic deafferentation depresses estrogen receptor levels in rat medial basal hypothalamus; (b) changes in noradrenergic transmission affect, via ?-adrenoceptors, the estradiol-induced increase of cytosol progestin receptor concentration in guinea pig hypothalamus; (c) cAMP increases testosterone aromatization in cultured neurons from turtle brain; (d) electrical stimulation of dorsal hippocampus augments, and reserpine or 6-hydroxydopamine treatment decrease, corticoid binding in cat hypothalamus. In the adenohypophysis changes in dopaminergic input after median eminence lesions or bromocriptine treatment of rats result in opposite modifications of pituitary estrogen receptor levels. Therefore all these observations support the view that neurotransmitters can modulate the attachment of steroid hormones to their receptors in target cells.

Cytosol estrogen and progestin receptors in endometrial carcinoma of patients treated with surgery, radiotherapy, and progestin. Clinical correlates.

Cytosol progestin (PR) and estrogen receptor (ER) concentrations were measured in 114 endometrial carcinoma specimens from 109 patients; these levels were correlated with clinical and histopathologic characteristics, and with clinical outcome in 44 patients followed for at least two years after the primary therapy consisting of surgery, irradiation and adjuvant administration of progestin. Eighty percent of all specimens were simultaneously PR- and ER-positive (greater than or equal to 6 fmol and greater than or equal to 3 fmol/mg protein, respectively) whereas 10% were both PR- and ER-negative. Early clinical stages (I and II) were more often receptor-positive, and the receptor concentration in these tumors was higher than in advanced or recurrent disease. The same was the case for superficial as compared with deeply invasive lesions. Both PR and ER concentrations in well or moderately differentiated tumors were higher than in anaplastic carcinomas. PR and ER concentrations did not correlate with the age of menopausal status, body weight or carbohydrate metabolism of the patients. In the patient group followed up for two years or more, the receptor-poor tumors tended to behave more aggressively than did receptor-rich malignancies in relation to patient survival. The measurement of PR and ER concentrations in advanced endometrial carcinoma has been proved useful in the selection of hormonal or cytotoxic chemotherapy. The current results advocate their use of prognostic risk factors which might be useful in selection of the most efficient treatment modalities for individual patients.

Cytosolic estrogen and progestin receptors in human endometrium from different regions of the uterus

The concentrations of cytosolic estrogen (ER) and progestin (PR) receptors are not identical in hyperplastic endometrium from different regions of the uterus. These receptor concentrations are 20–25 and 40–50% lower in the middle and isthmic uterine segments, respectively, than in the fundal part of this organ. From the clinical point of view, the minor differences in receptor concentrations between fundal and middle segments of the uterine body do not argue against the use of endometrial specimens obtained by curettage for evaluation of the receptor status of the endometrium.

Failure of protein synthesis inhibition to block progesterone desensitization of lordosis in female rats

Progesterone's desensitization effect on lordosis has been shown to correlate with a decreased concentration of hypothalamic progestin receptors after progesterone injection. In a recent study, one group of investigators found that the protein synthesis inhibitor anisomycin appeared to block progesterone's desensitization effect. Despite decreased levels of cytoplasmic progestin receptors, progesterone + anisomycin-treated rats exhibited a high level of lordosis four hr after a second progesterone injection. Because this finding conflicts with a progestin receptor model of progesterone's desensitization effect, we investigated it further. In the first experiments, ovariectomized rats were injected with estradiol benzoate followed 24 hr later by either progesterone or vehicle. Anisomycin injected 3 hr after progesterone, at a dose that causes inhibition of hypothalamic protein synthesis for at least 4 hr, was without effect on progesterone desensitization a day later. In other experiments silastic implants containing estradiol were inserted into ovariectomized rats. Forty-five hr later, rats received progesterone or vehicle, followed by injections of anisomycin or saline. Rats receiving anisomycin + progesterone were still highly receptive at 30 hr while saline + progesterone controls were not. Furthermore, the results were similar 4 hr after a second injection of progesterone at 30 hr. In a related experiment, we confirmed that anisomycin delayed dramatically termination of the period of sexual receptivity. In this laboratory anisomycin does not seem to block progesterone's desensitization effect. However, with certain procedures anisomycin delays the termination of sexual receptivity. Thus it is important in investigations of the mechanism of progesterone's desensitization effect that animals be tested prior to the second progesterone injection to determine if they are actually responding to the progesterone.

Alteration of sensitivity to progesterone facilitation of lordosis in guinea pigs by modulation of hypothalamic progestin receptors

In order to delineate further the role of the progestin receptor system in the hypothalamus-preoptic area in the regulation of lordisis in female guinea pigs, we injected estradiol benzoate and progesterone in various regimens that result in sensitivity to, desensitization to, or restoration of sensitivity to progesterone-facilitation of lordosis. We attempted to correlate the effectiveness of progesterone to facilitate lordosis with the effectiveness of progesterone to cause accumulation of nuclear progestin receptors measured by an in vitro [ 3H]R 5020 binding assay. A progesterone injection 40 h after an estradiol benzoate injection in ovariectomized guinea pigs resulted in lordosis in 83% of the animals, caused a 30% depletion of cytoplasmic progestin receptors and a 200% increase in the concentration of nuclear progestin receptors 4 h after injection compared with control animals. By 24 h after the injection, after the period of sexual receptivity had terminated, the concentration of nuclear progestin receptors was no longer elevated, and the concentration of cytoplasmic progestin receptors was decreased to a level 55% lower than control animals. This depression was due to a decrease in the concentration of binding sites, not to in vitro competition of the injected progesterone with the [ 3H]R 5020 because similar results were obtained with cytosol in which progesterone had been removed by gel filtration prior to incubation. These progesterone-injected guinea pigs did not respond to a second progesterone injection 24 h after the first (64 h), and the injection resulted in 70% fewer nuclear progestin receptors than in oil-injected controls. This decreased accumulation appears to be due to the decreased level of cytoplasmic progestin receptors brought about by the first progesterone injection. Estradiol benzoate injected concurrently with the first progesterone injection restored behavioral sensitivity to the second progesterone injection and caused 160% greater accumulation of nuclear progestin receptors in response to the second progesterone injection than control animals that had received only progesterone. The increased concentration of nuclear progestin receptors in the estradiol-injected animals appear to be due to increased availability of cytoplasmic progestin receptors. It seems that estradiol increases and progesterone decreases the concentration of cytoplasmic progesterone receptors in hypothalamus-preoptic area such that a subsequent injection of progesterone results in a high or low concentration of nuclear progestin receptors. The accumulation of sufficient nuclear progestin receptors in response to the progesterone injection may be a requirement in the process by which progesterone facilitates lordosis in estradiol-primed rodents.

Effects of tamoxifen, medroxyprogesterone acetate, and their combination on human endometrial estrogen and progestin receptor concentrations, 17β-hydroxysteroid dehydrogenase activity, and serum hormone concentrations

Short-term and long-term progestin exposures elicit secretory and atrophic changes, respectively, in the human endometrium. To understand the mechanisms for these diverse effects of progestins, we administered medroxyprogesterone acetate (100 mg daily orally) alone or together with the antiestrogen tamoxifen (20 mg daily) for 3 weeks (from the third through twenty-third day of the cycle) to healthy, normally cycling women. Medroxyprogesterone acetate administration led to atrophic changes in the endometrium and reduced the activity of endometrial 17β-hydroxysteroid dehydrogenase on the twenty-third day of the cycle below the values measured on the same day of the preceding control cycle. These changes were accompanied by decreased cytosol estrogen and progestin receptor concentrations, while the respective nuclear receptor levels remained unchanged. Since the diminished cytosol progestin receptor content could be the primary reason for the aforementioned results, the 3-week progestin treatment was supplemented with the antiestrogen tamoxifen, also known to be a partial estrogen agonist. This combination elicited, however, endometrial atrophy and an even more pronounced reduction in the 17β-hydroxysteroid dehydrogenase activity, although it increased cytosol progestin and nuclear estrogen receptor concentrations. Tamoxifen alone did not alter endometrial receptor concentrations or 17β-hydroxysteroid dehydrogenase activity. However, tamoxifen markedly increased circulating sex steroid concentrations, which changes were abolished by a concomitant medroxyprogesterone acetate administration. It thus appears that the initial and stimulatory effect of progestins on the endometrial function is relatively short-lived and that the later depressive actions of these steroids are achieved as soon as 3 weeks. Therapeutic implications of these findings are discussed.

Oestrogen induction of progestin receptors in the rat brain and pituitary gland: quantitative and kinetic aspects.

The processes of oestrogen-receptor binding, translocation and nuclear processing in the pituitary gland, preoptic area (POA), mediobasal hypothalamus (MBH) and amygdala were explored in relation to the induction of cytosol progestin receptors (PRc). Ovariectomized rats were injected i.v. with a single saturating dose (3·6 μg/kg body wt) of oestradiol-17β (OE2). At various times thereafter cytosol (ERc) and salt-extractable nuclear (ERn) oestrogen-receptor concentrations were determined by exchange assay. In all four tissues at 1 h after injection ERc fell and ERn increased, suggesting translocation of ERc into the nucleus. The extent of ERc depletion, however, was not identical in all tissues: substantially less depletion was observed in the amygdala (34%) and POA–MBH (56%) than in the pituitary gland (74%). Depletion of ERc was followed by a phase of replenishment, restoring ERc to preinjection values by 24 h. Concentrations of ERn in all tissues declined between 1 and 24 h, concomitant with the replenishment of ERc. Concentrations of PRc in the pituitary gland and POA–MBH increased during the first 12 h after injection of OE2 to a plateau value between 12 and 24 h, then declined to control values by 72 h. No induction of PRc was seen in the amygdala. A second injection of OE2 2 h after the first injection refilled the nuclear binding sites, restoring ERn to levels indistinguishable from those seen 1 h after a single OE2 treatment. The extent of ERc depletion after two injections with OE2 was, however, proportionately less than that seen after a single treatment with OE2. The second OE2 injection raised PRc concentrations above those seen after a single injection in the POA–MBH but not in the pituitary gland. When the two OE2 injections were more widely spaced (14 h apart) the PRc response in both the pituitary gland and POA–MBH was greater than after a single OE2 injection, and was comparable to that seen in animals given a very large dose (360 μg/kg body wt) of OE2. These results confirm the existence of differences between the pituitary gland, POA–MBH and amygdala in the ERc and PRc responses to oestrogen treatment. In addition, they suggest that the PRc response of the pituitary gland and POA–MBH to OE2 is influenced by previous exposure to OE2.

Progesterone in high doses may overcome progesterone's desensitization effect on lordosis by translocation of hypothalamic progestin receptors

The cellular mechanism by which progesterone desensitizes the central nervous sytem to further facilitation of lordosis by progesterone was studied. In the first experiment guinea pigs were injected with doses of estradiol benzoate and progesterone that result in refractoriness to further stimulation of lordosis by moderate doses of progesterone. Confirming previous reports, a large dose of progesterone was effective in overcoming this desensitization, resulting in lordosis responses. A lower dose of progesterone was ineffective in this regard. In subsequent experiments, cytosol and nuclear progestin receptors were measured in the hypothalamus-preoptic area and cerebral cortex with an in vitro exchange assay using [ 3H]R 5020 as the ligand. A high, effective dose of progesterone resulted in 46–48% higher levels of nuclear progestin receptors assayed in the hypothalamus-preoptic area than did a lower, ineffective dose. These results are consistent with the idea that progesterone injection in estradiol-primed rodents causes a subsequent desensitization to itself by decreasing the concentration of cytoplasmic progestin receptors in hypothalamus-preoptic area. A subsequent progesterone injection then results in a lower level of nuclear progestin receptors. Large doses of progesterone may overcome this desensitization by causing accumulation of levels of nuclear progestin receptors sufficient to facilitate lordosis.

Danazol has progestin-like actions on the human endometrium.

The administration of danazol, 200 mg three times daily, from the 3rd to the 23rd day of the cycle to normally menstruating women exhibited the following actions on the human endometrium: significantly reduced cytosol oestrogen and progestin receptor concentrations, and declined 17 beta-hydroxysteroid dehydrogenase activity. Very similar results were obtained during medroxyprogesterone acetate (100 mg daily) treatment for the same period of time. Danazol administration did not decrease circulating gonadotrophin levels but clearly suppressed luteal serum oestradiol and progesterone concentrations. Danazol was found to bind in vitro to endometrial progestin receptor with an affinity approximately 3% of that of progesterone. These findings are compatible with the notion that a local progestin-like rather than a systemic action of danazol is the way by which its therapeutic effect is exerted. This may be potentiated by the suppression of circulating oestradiol levels.

Estrogen and progestin receptors in intracranial meningiomas

Tissue samples from 16 meningioma patients were analysed for the cytosolic estrogen receptor concentration using isoelectric focusing and 11 of the 16 cases were also analysed for the cytosolic progestin receptor concentration using sucrose gradient centrifugation. In this study, 15 of the 16 (94%) and 9 of the 11 (82%) meningiomas had detectable estrogen and progestin receptors, respectively. The mean estrogen receptor concentration in female subjects was 8.9 fmol/mg protein and in males 3.0 fmol/mg protein. This sexual difference in receptor content was statistically significant. When the progestin receptor concentrations were plotted against the estrogen receptor concentrations in the same tumors, a relatively good positive correlation was obtained in female patients ( r = 0.87). These findings confirm and extend previous reports on the existence of sex steroid receptors in human brain tumors and might open up the possibility of selective endocrine therapy against meningiomas, especially in case of poorrisk patients.

Spontaneous canine mammary tumors: A model for human endocrine therapy?

Animal models for the study of mammary tumors usually involve the artificial induction of tumors by chemical or viral agents. Canine mammary tumors are, however, spontaneous. A comparison of the incidence, pathology and endocrine properties of dog and human breast tumors is therefore of interest in determining whether canine tumors can constitute a useful model for the study of clinical response to hormone therapy and whether, in recognized cases of hormone-dependence, pet bitches with mammary tumors should undergo endocrine therapy with synthetic hormones following mastectomy. Estrogen (ER) and progestin (PR) receptor concentrations were therefore assayed in mammary tumours from 144 bitches and 2 male dogs by a dextran-coated charcoal adsorption technique using [ 3H]-R 2858 and [ 3H]-R 5020 as radioligands. The incidence of ER and PR was analyzed according to the race, age, case history (number of pregnancies…) of the dogs and according to tumor size and type. About 1 3 rd of the tumors were classified as benign and 2 3 rds as malignant (WHO classification). Of the benign tumors, 32% had no receptor, 56% had both ER (10–124 fmol/mg protein) and PR (10–259 fmol/mg protein), 6% ER only and 6% PR only. Of the malignant tumors, 39% had no receptor, 44% had both ER (10–33 fmol/mg protein) and PR (10–90 fmol/mg protein), 9% ER only and 8% PR only.

Binding of estrogen and progestin in the human fallopian tube

The estrogen and progestin receptor concentrations in the human fallopian tube have been investigated. The binding of estrogen and progestin to their cytoplasmic and nuclear receptor proteins were of high affinity and specificity. The cytoplasmic and nuclear receptor concentrations in the isthmus, ampulla, and fimbria did not differ significantly. The nuclear progestin receptor concentrations in the isthmus and fimbriae were significantly higher (P less than 0.05) in the follicular phase than in the luteal phase of the menstrual cycle. In the postmenopausal tubes the receptor concentrations was low, whereas the progestin receptor concentration was quite high.