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PubMed1992

Influence of protein binding on the metabolic clearance rate of synthetic progestins in the rat liver perfusion model.

Levonorgestrel (LN), 3-Keto-desogestrel (KDG), norethisterone (NET), and gestodene (GST) were investigated in the recirculating rat liver perfusion model. Progestins were dissolved in buffered salt solution (MI), BSA containing (MII) or HSA and sex hormone binding globulin (SHBG) containing medium (MIII) at a concentration of about 60 ng/ml. Each 3-5 female rat livers were perfused with MI, MII, and MIII for 1 h. Perfusion medium, liver biopsies and total bile were analyzed for progestin levels by specific radioimmunoassays. Protein binding characteristics were determined in media and tissue. In all experiments bile (remaining liver) contained less than 1% (3%) of respective progestin dose demonstrating an almost complete biotransformation of all drugs by rat livers, irrespective of used medium. With MI, metabolic clearance rates (MCRs) and half-lives (t1/2) were not different for the four progestins. With MII, the actual progestin levels were generally higher than with MI, but half-lives were not changed. MCRs were close to the perfusion rate at the start of experiments but decreased to about 50%. MCRs of free and total drug levels were identical. Protein binding of 70-80% did not change with time. With MIII, the half-lives increased 1.5 fold (NET), 2.8 fold (KDG), 3.1 fold (GST) and 3.2 fold (LN) and MCRs accounted for 50-70% of perfusion rate at the beginning. The time courses of further MCR decreases were different for the various progestins and can be attributed to differences in specific binding of drugs to SHBG. Clearly, the presence of SHBG in MIII induced a shift of drug from liver tissue into the perfusion medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Modulation of the growth-inhibitory effects of progestins and the antiestrogen hydroxyclomiphene on human breast cancer cells by epidermal growth factor and insulin.

The molecular basis of the growth-inhibitory effects of progestins or antiestrogens in human breast cancer has not been fully elucidated. Both direct actions and indirect actions, where the growth inhibition results from modulation of the production of, and/or the response to, growth factors, have been proposed. In this study the ability of some growth factors to modulate progestin-induced inhibition of cell proliferation was investigated in vitro, using T-47D human breast cancer cells. When T-47D cells grown in insulin-containing medium were treated for 4 to 5 days with the synthetic progestin, ORG 2058, at a concentration of 10 nM, cell numbers were reduced to 10 to 20% of control. Simultaneous treatment with epidermal growth factor (EGF) and ORG 2058 led to a partial reversal of the growth-inhibitory effect of the progestin. The magnitude of the effect of EGF was concentration dependent, being half-maximal at 0.48 ng/ml (0.08 nM) and maximal at concentrations greater than 5 ng/ml (greater than 0.8 nM), where cell numbers were increased by 50% compared to those in the presence of ORG 2058 alone. ORG 2058 was no more potent in the absence of insulin, and, after several passages in insulin-free medium, addition of insulin failed to modulate the effect of ORG 2058. However, when maximal concentrations of insulin (5 micrograms/ml) and EGF (10 ng/ml) were administered together with ORG 2058, insulin and EGF appeared to act synergistically to reduce the ORG 2058-induced inhibition of proliferation. In similar experiments in which cells were treated with hydroxyclomiphene, a potent antiestrogen, insulin was shown to partially reverse the growth-inhibitory effects of hydroxyclomiphene. Significant increases in cell number above hydroxyclomiphene-treated controls were apparent at insulin concentrations greater than 50 ng/ml, and at 5 micrograms/ml the increase was approximately 2-fold. In contrast to the situation with progestins, simultaneous treatment with EGF and insulin had only an additive effect in reversing the growth-inhibitory effect of the antiestrogen. The results are compatible with the hypothesis that part of the growth-inhibitory effects of progestin and antiestrogen on human breast cancer cell proliferation is mediated by inhibition of autocrine growth factor production. However, they do not exclude more direct mechanisms involving modulation of progesterone and/or estrogen receptors by EGF and/or insulin.(ABSTRACT TRUNCATED AT 400 WORDS)

Breast Neoplasms↗

PubMed1982

Regulation of ovarian progestin production by epidermal growth factor in cultured rat granulosa cells.

The modulation of ovarian steroidogenesis by epidermal growth factor (EGF) was investigated in cultured rat granulosa cells. Granulosa cells, obtained from ovaries of immature, hypophysectomized, estrogen-treated rats, were incubated for 2 days with EGF, follicle-stimulating hormone (FSH), or EGF plus FSH. Treatment with EGF did not affect estrogen production, but stimulated progestin (i.e. progesterone and 20 alpha-hydroxy-pregn-4-en-3-one) production in a dose-dependent manner. Stimulation of progestin production by EGF appears to be the result of an increase in pregnenolone biosynthesis as well as increases in the activities of 20 alpha-hydroxysteroid dehydrogenase and 3 beta-hydroxysteroid dehydrogenase/isomerase. Treatment with FSH increased both estrogen and progestin production by cultured granulosa cells. When cells were treated concomitantly with EGF, FSH-stimulated estrogen production was inhibited, while progestin production was further enhanced. The EGF enhancement of FSH-stimulated progestin production appears to be the result of synergistic increases in pregnenolone biosynthesis and 20 alpha-hydroxysteroid dehydrogenase activity, resulting in substantial increases in 20 alpha-hydroxypregn-4-en-3-one but not progesterone production. The effects of EGF were shown to be time-dependent. The concept of a direct action of EGF on rat granulosa cells is reinforced by the demonstration of high affinity (Kd approximately 3 X 10(-10) M), low capacity (approximately 5,000 sites/cell) EGF binding sites in these cells. Thus, EGF interacts with specific granulosa cell receptors to stimulate progestin but to inhibit estrogen biosynthesis.

Animals↗

PubMed1995

Combined estrogen and progestin hormone replacement therapy in relation to risk of breast cancer in middle-aged women.

OBJECTIVE: To determine the risk of breast cancer in relation to the use of combined estrogen and progestin hormone replacement therapy (HRT). DESIGN: A population-based case-control study. SETTING: The general female population of King County in western Washington State. PARTICIPANTS: Middle-aged (50 to 64 years) women, including 537 patients with incident primary breast cancer diagnosed between January 1, 1988, and June 30, 1990, who were ascertained through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results cancer registry and 492 randomly selected control women without a history of breast cancer. MAIN OUTCOME MEASURE: Breast cancer risk in relation to use of menopausal hormones. RESULTS: Menopausal hormones of some type had been used by 57.6% of breast cancer cases and 61.0% of comparison women. The women who had ever taken combined estrogen-progestin HRT, representing 21.5% of cases and 21.3% of controls, were not at increased risk of breast cancer (relative odds [RO] = 0.9; 95% confidence interval [CI], 0.7 to 1.3). Compared with nonusers of menopausal hormones, those who used estrogen-progestin HRT for 8 or more years had, if anything, a reduced risk of breast cancer (RO = 0.4; 95% CI, 0.2 to 1.0). CONCLUSIONS: On the whole, the use of estrogen with progestin HRT does not appear to be associated with an increased risk of breast cancer in middle-aged women. Nonetheless, since the use of combined estrogen-progestin HRT has only recently become prevalent, future investigations must assess whether breast cancer incidence is altered many years after estrogen-progestin HRT has been initiated, particularly among long-term users.

Breast Neoplasms↗

PubMed1995

Endometrial squamous metaplasia. An unusual response to progestin therapy of hyperplasia.

OBJECTIVE: To report the finding of squamous metaplasia within endometrial glands occurring as a result of progestin therapy of hyperplasia. DESIGN: Case series. Retrospective analysis of two cases from 9235 accessioned endometrial biopsies. SETTING: Hospital-based pathology laboratory processing inpatient and outpatient specimens. PATIENTS: Two women, ages 49 and 34 years, with endometrial hyperplasia without squamous metaplasia who were treated with progestin. RESULTS: Extensive squamous metaplasia was found in endometrial glands following progestin therapy. The post-therapy biopsies also showed progestin-related alterations but no evidence of active hyperplasia. CONCLUSION: Squamous metaplasia in these cases appears to be a consequence of progestin therapy. The absence of hyperplasia in the progestin-treated endometrium suggests that the squamous metaplasia does not represent persistence or progression of the original hyperplastic lesion.

Adult↗

PubMedDate not supplied

Effect of progestin treatment on estradiol-and growth factor-stimulated breast cancer cell lines.

BACKGROUND: Reports about the effects of progestins on cell proliferation are contradictory. We investigated the effect of progesterone, medroxyprogesterone acetate, megestrol acetate, ORG 2058 and the antiprogestin RU 486 on two hormone-dependent cell lines, T47D and MCF-7 (characterized by a different content of PgR). The aim of the study was to understand the eventual ability of progestins to interfere with cell proliferation stimulated by estradiol and various growth factors (TGF-a, IGF-I, IGF-II). MATERIAL AND METHODS: MCF-7 and T47D cells were maintained in DMEM/F12 medium supplemented with 2% FCS while experiments were carried out in the same culture medium using DCC-stripped FCS. RESULTS: In the absence of estradiol, all tested progestins generally tended to stimulate cell growth in the T47D cell line, but in the MCF-7 cell line only the highest concentrations (10(-6) M and 10(-7) M) were found to be stimulatory. In contrast, in the presence of 10(-8) M estradiol, progestins tended to inhibit cell growth stimulation in MCF-7 and T47D cell lines. The antiprogestin RU 486 exerted a stimulatory effect similar to that promoted by estradiol itself in MCF-7 cells. Instead, in T47D cells, RU 486 did not modify cell growth in the absence of estradiol, but tended to counteract the estradiol-promoted cell proliferation. In MCF-7 cells, medroxyprogesterone acetate and megestrol acetate were also able to effectively counteract the cell growth induced by TGF-alpha. However, none of these progestins was able to abolish cell proliferation promoted by IGF-I or IGF-II. CONCLUSION: We therefore concluded that failure to respond to progestin treatment may be due to the very heterogeneous nature of human breast tumors and to the inability of these molecules to interfere with the IGF-R pathway.

Adenocarcinoma↗

PubMed1997

[Progestins and the endometrium].

Natural progesterone and synthetic progestins lead in the endometrium to the inhibition of mitosis, reduction of estrogens and progesterone receptors and decidualisation of the endometrium. This latter process seems to be of main importance for the implantation. Furtheron, progesterone and progestins induce the formation of IGF-binding proteins (IGFBP's), which for instance lead to the binding of IGF-1 and thereby to a reduction of proliferative or mitogenic effects of the estrogens on the endometrium. In addition, progesterone or progestins induce or inhibit a number of other factors. Among others, protein PP 14 is induced in the endometrium by progesterone or progestins. This protein has immunological properties. While on the one hand the enzyme glutathionperoxydase is blocked, there is on the other hand an induction of transglutamase activity. Furthermore, progestins in high doses lead to a reduction of the microvasculature and a dilatation of the venoles. Therefore, progesterone and progestins are best suited for treatment and prevention of abnormal proliferation of the of the endometrim even up to carcinoma in situ or endometrial cancer. For this, the severity of endometrial changes and the age of the patients have to be taken into account. This also applies to the prevention of pathological endometrial changes.

Cell Division↗

PubMed2000

Estrogen and progestin, lipoprotein(a), and the risk of recurrent coronary heart disease events after menopause.

CONTEXT: Lipoprotein(a) [Lp(a)] has been identified as an independent risk factor for coronary heart disease (CHD) events. However, few data exist on the clinical importance of Lp(a) lowering for CHD prevention. Hormone therapy with estrogen has been found to lower Lp(a) levels in women. OBJECTIVE: To determine the relationships among treatment with estrogen and progestin, serum Lp(a) levels, and subsequent CHD events in postmenopausal women. DESIGN AND SETTING: The Heart and Estrogen/progestin Replacement Study (HERS), a randomized, blinded, placebo-controlled secondary prevention trial conducted from January 1993 through July 1998 with a mean follow-up of 4.1 years at 20 centers. PARTICIPANTS: A total of 2763 postmenopausal women younger than 80 years with coronary artery disease and an intact uterus. Mean age was 66.7 years. INTERVENTION: Participants were randomly assigned to receive either conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, in 1 tablet daily (n = 1380), or identical placebo (n = 1383). MAIN OUTCOME MEASURES: Lipoprotein(a) levels and CHD events (nonfatal myocardial infarction and CHD death). RESULTS: Increased baseline Lp(a) levels were associated with subsequent CHD events among women in the placebo arm. After multivariate adjustment, women in the second, third, and fourth quartiles of baseline Lp(a) level had relative hazards (RHs) (compared with the first quartile) of 1.01 (95% confidence interval [CI], 0.64-1.59), 1.31 (95% CI, 0.85-2.04), and 1.54 (95% CI, 0.99-2.39), respectively, compared with women in the lowest quartile (P for trend = .03). Treatment with estrogen and progestin reduced mean (SD) Lp(a) levels significantly (-5.8 [15] mg/dL) (-0.20 [0.53] micromol/L) compared with placebo (0.3 [17] mg/dL) (0.01 [0.60] micromol/L) (P<.001). In a randomized subgroup comparison, women with low baseline Lp(a) levels had less benefit from estrogen and progestin than women with high Lp(a) levels; the RH for women assigned to estrogen and progestin compared with placebo were 1.49 (95% CI, 0.97-2.26) in the lowest quartile and 1.05 (95% CI, 0.67-1.65), 0.78 (0.52-1.18), and 0.85 (0.58-1.25) in the second, third, and fourth quartiles, respectively (P for interaction trend = .03). CONCLUSIONS: Our data suggest that Lp(a) is an independent risk factor for recurrent CHD in postmenopausal women and that treatment with estrogen and progestin lowers Lp(a) levels. Estrogen and progestin therapy appears to have a more favorable effect (relative to placebo) in women with high initial Lp(a) levels than in women with low levels. This apparent interaction needs confirmation in other trials.

Aged↗

PubMed2003

Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial.

CONTEXT: In the Women's Health Initiative trial of estrogen-plus-progestin therapy, women assigned to active treatment had fewer fractures. OBJECTIVE: To test the hypothesis that the relative risk reduction of estrogen plus progestin on fractures differs according to risk factors for fractures. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial (September 1993-July 2002) in which 16 608 postmenopausal women aged 50 to 79 years with an intact uterus at baseline were recruited at 40 US clinical centers and followed up for an average of 5.6 years. INTERVENTION: Women were randomly assigned to receive conjugated equine estrogen, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOME MEASURES: All confirmed osteoporotic fracture events that occurred from enrollment to discontinuation of the trial (July 7, 2002); bone mineral density (BMD), measured in a subset of women (n = 1024) at baseline and years 1 and 3; and a global index, developed to summarize the balance of risks and benefits to test whether the risk-benefit profile differed across tertiles of fracture risk. RESULTS: Seven hundred thirty-three women (8.6%) in the estrogen-plus-progestin group and 896 women (11.1%) in the placebo group experienced a fracture (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.69-0.83). The effect did not differ in women stratified by age, body mass index, smoking status, history of falls, personal and family history of fracture, total calcium intake, past use of hormone therapy, BMD, or summary fracture risk score. Total hip BMD increased 3.7% after 3 years of treatment with estrogen plus progestin compared with 0.14% in the placebo group (P<.001). The HR for the global index was similar across tertiles of the fracture risk scale (lowest fracture risk tertile, HR, 1.20; 95% CI, 0.93-1.58; middle tertile, HR, 1.23; 95% CI, 1.04-1.46; highest tertile, HR, 1.03; 95% CI, 0.88-1.24) (P for interaction =.54). CONCLUSIONS: This study demonstrates that estrogen plus progestin increases BMD and reduces the risk of fracture in healthy postmenopausal women. The decreased risk of fracture attributed to estrogen plus progestin appeared to be present in all subgroups of women examined. When considering the effects of hormone therapy on other important disease outcomes in a global model, there was no net benefit, even in women considered to be at high risk of fracture.

Aged↗

PubMed1997

Progestin alone as primary treatment of endometrial carcinoma in premenopausal women. Report of seven cases and review of the literature.

BACKGROUND: The standard treatment for endometrial carcinoma is staging laparotomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy. In an attempt to preserve childbearing potential, selected patients with endometrial carcinoma were treated with progestin alone as primary therapy. METHODS: Patients were identified through searches of tumor registries and solicitation of consulting gynecologic oncologists at the affiliated institutions of the University of California-Los Angeles Center for the Health Sciences. Only those patients with a diagnosis of endometrial carcinoma treated with progestin alone as primary therapy were included in the study. Independent pathologic review was performed by a recognized expert gynecologic pathologist to exclude cases of endometrial hyperplasia. A MEDLINE search was conducted to identify reports of similarly treated patients. RESULTS: Seven patients were treated with progestin alone for endometrial carcinoma at the study institution. Fourteen additional patients were identified through the literature search. Combining the data for all patients, 13 of 21 patients (62%) had an initial response to progestins. Three initial responders later developed recurrent disease, one of whom was found to have extrauterine disease at laparotomy. Eight of 21 patients (38%) did not respond to progestins and underwent more definitive treatment. None of these patients later developed recurrent disease. Six viable infants were delivered of three patients after therapy. Nineteen of 21 patients were alive without evidence of disease at last follow-up. CONCLUSIONS: The results of this study show that premenopausal women with endometrial carcinoma may be treated successfully with progestin therapy alone as primary therapy to preserve childbearing potential.

Adenocarcinoma↗

PubMed1993

Immunocytochemical localization of midbrain estrogen receptor- and progestin receptor-containing cells in female guinea pigs.

In the guinea pig midbrain, a low concentration of progestin receptors is induced by estradiol. This is in contrast to the mediobasal hypothalamus which has a large number of estradiol-induced progestin receptors. Because the midbrain is an important site for the hormonal regulation of sexual behavior, we mapped the distribution of cells containing estrogen receptor- and estradiol-induced progestin receptor-immunoreactivity in that area. Estrogen receptor-immunoreactive cells are found in midbrain sites previously reported, including the midbrain central gray, the tegmentum lateral and ventral to the central gray, peripeduncular region, and parabrachial nuclei. While progestin receptor-immunoreactive cells were not detected without estradiol priming, estradiol-induced progestin receptors were found throughout the rostrocaudal extent of the midbrain central gray and adjacent tegmental area. Progestin receptor-immunoreactive cells were far fewer than estrogen receptor containing cells, had less cytoplasmic staining, and appeared restricted to the midbrain central gray, lateral and ventrolateral to the cerebral aqueduct and the adjacent tegmental area.

Animals↗

PubMed1991

Short-term effects of estrogen and progestin on blood pressure of normotensive postmenopausal women.

Blood pressure rises in women with increasing age, possibly related to the decrease in production of female hormones that accompanies menopause. Although estrogen or progestin administration alone consistently does not lower blood pressure in postmenopausal women, possible interactions of these two hormones in affecting blood pressure are not well understood. We studied 12 surgically postmenopausal, normotensive women, aged 51 +/- 2 years (SEM). Treatment for each subject consisted of 1 week each of placebo, estrogen (conjugated equine estrogens, 2.5 mg/day), progestin (medroxyprogesterone acetate, 60 mg/day), and combined estrogen and progestin, given in varied order. At the end of each week, auscultatory blood pressures were measured while patients were seated. Neither estrogen nor progestin alone either increased or decreased blood pressure significantly, whereas combined estrogen and progestin lowered systolic, diastolic, and mean blood pressures 6 to 7 mm Hg (P less than .05). Treatment order was unrelated to the change in blood pressure values. The authors suggest that administering progestin with estrogen may be more effective in lowering blood pressure than either hormone alone in postmenopausal women.

Blood Pressure↗

PubMed1993

Expression of 67 kDa laminin receptor in human breast cancer cells: regulation by progestins.

The level of 67 kDa laminin receptor (67LR) expression on breast and colon tumor cell surfaces was previously shown to be correlated with the capacity of tumor cells to metastasize. In the present work we investigate the effects of progestins and estrogen on the expression of 67LR in two sublines of the T47D human breast cancer cells: weakly tumorigenic, poorly invasive parental T47D cells and a highly tumorigenic, more invasive T47Dco subclone. Immunoblotting with an affinity purified antibody directed against a synthetic peptide recognizes the 67LR in these cells. 67LR expression in the T47Dco subclone is 5.5-fold higher than in their parental T47D cells. Treatment of T47D cells with 1 nM of the synthetic progestin R5020 results in a 4-fold increase in 67LR protein expression. Estrogen also induced 67LR expression, but only by 1.5-fold. The progestin-stimulated expression of the 67LR correlates with a 4.3-fold increase in attachment of T47D cells to laminin. A monoclonal antibody, mAb 13, directed against beta 1 integrin, completely blocks the attachment of T47D cells to fibronectin, only partially inhibits the attachment of T47D cells to laminin, and appears not to affect the progestin-stimulated laminin attachment of T47D cells. A new antiprogestin, ZK 112.993, significantly inhibits both progestin-stimulated 67LR expression and the increased attachment to laminin. These results suggest a possible role for progestin in mediating one of the multiple events thought to be important in metastasis of steroid receptor positive human breast cancer cells.

Analysis of Variance↗

PubMed1991

Progestin treatment depresses estrogen receptor but not cathepsin D levels in needle aspirates of benign breast disease.

We studied the effect of a progestin (lynestrenol) on estrogen receptors (ER) and cathepsin D (cath-D) levels immunochemically in successive fine needle aspirates of benign breast disease. Fibrocystic disease was the main pathology (43 out of 47 patients). Thirty-one patients were treated with 10 mg of lynestrenol daily from the fifth to the twenty-fifth day of the menstrual cycle for 1 to 3 months. Sixteen untreated patients were used as controls. Lynestrenol significantly decreased the percentage of ER stained cells. This is in agreement with the antiestrogenic effect of progestin and, for the first time, indicates that in vivo progestin may decrease the stimulatory effect of estrogens on mammary cells by decreasing their estrogen receptor content. No effect of progestin on cath-D level was found throughout the whole population. However, this level varied more between aspirates of each patient in the treated group than in the control group, suggesting heterogeneity in patient responses to progestin. Since cath-D may have a role in carcinogenesis, clinical follow-up of these patients and more detailed studies are required to determine whether this progestin-challenge test has any value for detecting high risk mastopathies and for predicting effectiveness of treatment.

Adult↗

PubMed1979

Estrogen-sensitive progestin-binding sites in the female rat brain and pituitary.

The following properties of the cytoplasmic progestin receptor were studied in the hypothalamus, cortex, pituitary and uterus of the estrogen-primed castrated adult female rat using the highly potent progestin R 5020 (promegestone). (a) Sedimentation pattern. In sucrose density gradients, the R 5020-progestin receptor complex sedimented with a coefficient of about 6 to 7S. (b) Binding parameters. R 5020 bound to the progestin receptor with an intrinsic dissociation constant of about 10(-9) M as measured by a Dextran-coated charcoal (DCC) technique. The number of binding sites, however, differed widely. (c) Specificity. Only progestins competed for [3H]R 5020 binding. (d) Estrogen-dependency. In both immature and castrated adult rats, estrogen administration increased the number of R 5020-specific binding sites, assayed in vitro by a DCC technique, in the uterus, pituitary and hypothalamus, but not in the amygdala, hippocampus nor in the cortex. The increase was maximum between 40 and 48 h after priming with the potent estrogen, moxestrol, and could not be induced by androgens nor by progestins.

Adrenalectomy↗

PubMed1984

Inhibition of sexual behavior in female guinea pigs by a progestin receptor antagonist.

The new steroidal progestin receptor antagonist, RU 38486, was used to determine if progesterone-facilitation of sexual behavior in female guinea pigs requires interaction of the hormone with neural progestin receptors. Five milligrams but not 0.5 mg RU 38486 inhibits the expression of sexual behavior in ovariectomized, estrogen-primed guinea pigs treated with 0.1 mg progesterone. This inhibition can be overcome by administration of a large dose of progesterone, suggesting that the drug-effect is specific to the progestin receptor system. RU 38486 binds, in vitro, to progestin receptors and decreases the availability of hypothalamic progestin receptors in estrogen-treated guinea pigs. These studies provide strong evidence that progesterone interaction with intracellular neural progestin receptors mediates the facilitation of sexual behavior by progesterone in female guinea pigs.

Animals↗

PubMed1990

Prazosin treatment does not affect progestin receptor induction in microdissected regions of the rat hypothalamus.

Sex differences in estrogen-induced progestin receptors have been described in specific regions of the rat brain. To determine if alpha 1-neurotransmission plays a role in the expression of the sex differences in progestin receptor induction, the effects of the alpha 1-antagonist, prazosin, on progestin binding in microdissected regions of the rat brain was determined. Adrenalectomized/gonadectomized male or female rats were administered various doses of estradiol benzoate (EB) in combination with prazosin. With all treatment paradigms, and in both sexes, no significant effect of prazosin treatment on progestin receptor levels was observed. These results are consistent with the idea that sex differences in the estrogen-induction of progestin receptors in the rat hypothalamus are not due to sex differences in the alpha 1-adrenergic regulation of progestin receptor synthesis.

Adrenergic Fibers↗

PubMed1988

Effects of modulating neonatal progestins and androgens on the development of play and other social behavior in the rat.

Rough-and-tumble play is sexually dimorphic in many species of mammals. Effects of androgen exposure on this behavior have been well documented, although the possible role of other hormones is less well known. This paper reports experiments in a series designed to investigate effects of neonatal exposure to progestins on the development of juvenile play behavior in rats. Specifically, the effects of altering levels of progestins and androgens in combination on the subsequent development of play behavior was studied, in order to investigate further the mechanism of progestogenic effects. We have previously [L. I. A. Birke and D. Sadler (1984). Physiol. Behav. 33, 217-219] reported an apparently anomalous effect of lowering endogenous progesterone using the antiserum given postnatally; this was predicted to raise levels of juvenile play. The prediction was, however, supported only for males; treated females showed lower levels of play than controls. The present study was designed to investigate these effects further, and to test hypotheses about the mode of action of neonatal progestins. Using various combinations of neonatal progestins (progesterone or medroxy-progesterone acetate, MPA), and testosterone or the antiserum to testosterone, we analyzed the amounts of play and other social behavior shown by juvenile rats. The data support a hypothesis that the previously reported effects of progestin exposure on play result from weakly androgenic actions of the progestins, which presumably compete with other androgens in males. The cellular mechanisms involved are, however, unknown.

Agonistic Behavior↗