Micrograms Of Estradiol Benzoate Research Articles

LH response to LH-RH neonatally estrogenized male rats.

The LH response to 100 or 1000 ng of LH-RH was studied in adult male rats treated neonatally with 500 micrograms of estradiol benzoate or olive oil. The dose of 100 ng elicited the same LH increase in both groups, but the estrogenized animals responded more when 1000 ng of LH-RH was injected. These data suggest that the decreased LH response to orchidectomy found in estrogenized animals is not due to a failure in pituitary responsiveness to LH-RH.

Differences in Prepuberal Neonatally Estrogenized or Androgenized Male Rats

The main objective of this work was to analyze the different effects produced in prepuberal male rats by neonatal androgenization or estrogenization. For this purpose male Wistar rats were injected on day one of life with 500 micrograms of estradiol benzoate (estrogenized animals), 500 micrograms of testosterone propionate (androgenized animals) or olive oil (control animals) and decapitated on day 15. At the moment of decapitation estrogenized animals showed decreases in body, testes, prostate and adrenal weights, increases in pituitary, seminal vesicles and epididymis weights, an increase in prolactin plasma levels and a decrease in those of androgens. Androgenized animals showed only decreased testes and epididymis weights and androgen plasma levels. These results evidence the presence of important qualitative differences in prepuberal neonatally estrogenized or androgenized rats, especially in the accessory sex organs.

Effect of estradiol benzoate on the pituitary-gonadal axis in the intact male rat.

Adult male rats were treated with 50 microgram of estradiol benzoate daily for 28 days. The sex organs and pituitary weights showed changes classically associated with estrogen treatment. Both plasma and testicular testosterone levels diminished to almost trace level 24 hours after the first estrogen injection and remained at that level throughout the experimental period. The pituitary LH levels and concentration showed a progressive decline; however, the plasma LH levels remained unchanged throught the experimental period. These findings suggest that in intact adult males, estrogen affects testicular testosterone production directly. These observation suggests the necessity for reevaluation of the current concepts concerned with testis-pituitary feedback mechanisms.

The in vitro inhibitory action of antiprogestin RU486 on LH and FSH secretion in the absence of progesterone in rats is estrogen-dependent.

Previous in vivo findings show that in the virtual absence of progesterone (P), the antiprogestin RU486 reduces LH and FSH secretion in proestrous rats, indicating that activation of P receptor (PR) can occur in the absence of the cognate ligand. The present study investigates, in vitro, whether or not the inhibitory effect of antiprogestin RU486 on gonadotropin secretion in the absence of P is estrous cycle dependent, and whether its specific expression in proestrus mirrors the high estrogen (E2) background. In the first experiment we investigated the effect of RU486 (10 nM) and/or LHRH (10 nM) on LH and FSH secretion in incubated pituitaries collected on each day of the estrous cycle of the rat. In the second experiment, we determined the effect of RU486 and/or LHRH on preovulatory LH and FSH release by pituitaries from female rats that were ovariectomized (OVX), treated with the antiestrogen LY117018-HCL (Eli Lilly & Co.), or injected with 20 micrograms of estradiol benzoate (EB). The third experiment investigated the effect of RU486 and/or LHRH on LH and FSH release by pituitaries collected from intact or EB-treated (0.1 mg/kg over three consecutive days) male rats. RU486 reduced both basal and LHRH-stimulated LH and FSH secretion in proestrous pituitaries from normal 4-day cyclic rats. By contrast, in diestrous pituitaries, RU486 increased both parameters of LH secretion but was without effect on FSH release. RU486 was also without effect in pituitaries collected from rats in estrus or metestrus, or from OVX or antiestrogen-treated rats. Moreover, EB injection or treatment induced the full inhibitory effect of RU486 in pituitaries from female and male rats, respectively. The above results suggested that P occupancy of the receptor is not required for the formation or function of the active receptor and hence for preovulatory LH and FSH secretion, and that this form of PR activation at pituitary level is E2-dependent and not genetically determined.

Deciliation in the ampulla of the rat oviduct and effects of estrogen on the process

The mechanism by which cells in the ampullae of the rat oviducts undergo rapid deciliation during each estrous cycle and the effects of estrogen on the ciliated cells were examined. Untreated rats were killed on each day of the 5-day estrous cycle, and the ampullae of their oviducts were removed. Other rats were injected subcutaneously each day for 5 days with 0.3 microgram or 3.0 micrograms of estradiol benzoate or with 0.3 mg of tamoxifen, an estrogen antagonist, per kilogram of body weight. The ampullae of the oviducts of the treated rats were excised on the day following the last injection. The tissues from all the rats were fixed in glutaraldehyde, stained with uranyl acetate and lead citrate, and examined with a transmission electron microscope. Deciliation of cells was seen to occur by membrane-bound cilia packets (CPs) forming at the apices of cells and pinching off. Although CPs were more numerous at proestrus, they were also observed at estrus, diestrus-1, and diestrus-2, suggesting that the process of deciliation is an ongoing one that merely changes in rate. No evidence of resorption of cilia was seen. Estradiol treatment did not prevent CPs from forming, nor was tamoxifen treatment associated with any apparent enhancement of deciliation. Ciliated cells with CPs stained more darkly than ciliated cells that were without CPs, and the former appeared similar in their staining characteristics to secretory cells, most of which stain darkly. It was concluded that the cells of the ampulla deciliate rapidly by shedding their cilia into the lumen of the oviduct, that estrogen does not halt the process, and that ciliated cells may be transformed to secretory cells following loss of their cilia.

The positive feedback action of estrogen mobilizes LH-containing, but not FSH-containing secretory granules in ovine gonadotropes.

It has previously been shown in the ewe that luteinizing hormone (LH)-containing secretory granules become polarized to the side of the gonadotrope nearest to a vascular sinusoid during the preovulatory period. We have used laser scanning confocal microscopy to monitor the migration of LH and follicle stimulating hormone (FSH)-containing secretory granules in the gonadotrope of the ewe. Ovariectomized (OVX) ewes (n = 4/group) were given either 50 micrograms of estradiol benzoate (EB) or oil and were killed 16 h later for collection of the pituitary glands for immunohistochemistry and confocal microscopy. Pituitary sections were simultaneously immunolabelled for LH and FSH and were visualized on the same sections using fluorescent markers. All cells that contained LH also contained FSH and vice versa. The results showed that LH-containing granules were uniformly distributed throughout the cytoplasm in 83% of gonadotropes from controls, while in the remaining 17% the granules were predominantly located adjacent to the plasma membrane. Following EB treatment, LH-containing secretory granules were distributed around the plasma membrane in 84% of immunopositive gonadotropes; FSH remained uniformly distributed throughout the cytoplasm. We conclude that estrogen causes the movement of LH-containing granules to the plasma membrane in gonadotropes but does not influence the distribution of FSH-containing granules. Rather than being polarized to one side of the cell, the LH-containing granules were distributed around the periphery of the cell.

Estradiol regulation of alpha 1b-adrenoceptor mRNA in female rat hypothalamus-preoptic area.

Estradiol treatment for 48 h increases the density of alpha 1B-adrenoceptors in the hypothalamus-preoptic area of ovariectomized female rats by five- to six-fold. Present studies tested the hypothesis that estradiol elevation of hypothalamus-preoptic area alpha 1B-adrenoceptor density is correlated with increased levels of mRNA for this receptor. We developed a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) protocol for measuring brain alpha 1b-adrenoceptor mRNA. The primers chosen yielded the predicted 409 base pair PCR product when used to amplify authentic alpha 1b-adrenoceptor cDNA. The identity of the RT-PCR products from rat brain was confirmed by restriction digest analysis and sequencing. Moreover, there was a good correlation between the levels of alpha 1b-adrenoceptor mRNA measured by RT-PCR in liver, whole brain and cerebellum with previous measurements using Northern blots and RNAse protection assays. We then performed RT-PCR on total RNA from hypothalamic-preoptic area tissue taken from ovariectomized control rats and from ovariectomized rats injected once or twice with 2 micrograms of estradiol benzoate at 24 or 24 and 48 h before sacrifice. Exposure to estradiol for either 24 or 48 h significantly increased levels of alpha 1b-adrenoceptor mRNA by 86-110% in the hypothalamus-preoptic area of ovariectomized female rats when compared to oil-treated controls. We also examined whether estradiol regulates alpha 1b-adrenoceptor mRNA in the cortex. Cortical alpha 1b-adrenoceptor mRNA levels were reduced to approximately 20% of control levels when measured 24 h after hormone injection. A similar decrease in cortical alpha 1b-adrenoceptor mRNA was observed 48 h after estrogen administration. In summary, estradiol treatment significantly increases the level of alpha 1b-adrenoceptor mRNA in the hypothalamus-preoptic area, a brain region involved in the control of reproductive function. In the cortex, a brain region with relatively few estrogen receptors, the same estrogen treatment reduces alpha 1b-adrenoceptor mRNA levels.

Colocalization of NADPH-diaphorase and estrogen receptor immunoreactivity in the rat ventromedial hypothalamic nucleus: stimulatory effect of estrogen on NADPH-diaphorase activity.

NADPH-diaphorase (NADPH-d) histochemistry was combined with estrogen receptor (ER) immunohistochemistry in order to study effect of estrogen on NADPH-d activity and establish an anatomical relationship between NADPH-d and ER-immunoreactivity (ir) containing neurons in the ventromedial hypothalamic nucleus (VMN). Gonadectomized female and male rats received either oil (control group) or 10 micrograms of estradiol benzoate (EB) for two successive days and were sacrificed on day 4. While NADPH-d histochemistry stained a specific subpopulation of neurons in the ventrolateral portion of the VMN of all groups, there was a marked sex difference in the effect of EB treatment. EB elevated the number of NADPH-d positive neurons in females but had no significant effect in males. Double-labeling histochemistry revealed that more than 70% of the NADPH-d positive neurons contained ER-ir in the VMN of all groups, with EB-treated females having a significantly higher frequency than all other groups. Since neuronal NADPH-d is nitric oxide synthase (NOS), these results provide anatomical evidence for an association of estrogen with NOS in the rat VMN and suggest that NOS activity can be modulated by estradiol in estrogen sensitive neurons.

Decreased availability of metabolic fuels suppresses estrous behavior in Syrian hamsters.

The availability of oxidizable metabolic fuels affects reproductive physiology and behaviors in female mammals. In Syrian hamsters, 48 h of food deprivation is sufficient to suppress secretion of gonadotropins and ovarian steroids and to prevent the occurrence of ovulation and estrous behavior. These experiments attempted to determine whether the deprivation-induced suppression of lordosis is entirely due to the disruption of ovarian steroid secretion or whether there are also changes in behavioral responsiveness to estradiol and/or progesterone (P). Estrous behavior was induced in ovariectomized hamsters with sequential injections of 5 micrograms of estradiol benzoate (EB) and 200 micrograms P. Food deprivation for 48 h, either before or just after EB treatment, significantly suppressed the amount of time females spent in lordosis during a 5-min test with a sexually experienced male. Treatment with an inhibitor of glycolysis (2-deoxy-D-glucose) in combination with an inhibitor of fatty acid oxidation (methyl palmoxirate) for 48 h mimicked the effects of food deprivation and suppressed the amount of time spent in lordosis after treatment with EB+P. Given alone, neither metabolic inhibitor had an effect on lordosis. These findings indicate that suppression of hamster estrous behavior by metabolic fuel deprivation is at least in part due to a reduced responsiveness to estradiol and/or progesterone. Furthermore, estrous behavior is responsive to metabolic fuels in general. This is unlike hamster ovulatory cycles, which are primarily responsive to glucose availability.

Effects of Intraventricular Implantation of Crystalline Estradiol Benzoate on the Sleep‐Wakefulness Orcadian Rhythm of Ovariectomized Rats

The effect of estrogen on the sleep-wakefulness circadian rhythm was examined in ovariectomized rats. Implantation of crystalline estradiol benzoate (EB) into the third cerebral ventricle reduced the slow wave sleep (SWS) and paradoxical sleep (PS) appearances within the dark period. This result was similar to that obtained by a systemic administration of 20 micrograms of EB. The inhibition of sleep during the nighttime was more remarkable in PS than in SWS. The reduction of SWS was due to a shorter duration of SWS episodes and the reduction of PS to a fewer number of PS episodes. These results indicate that ovariectomized rats treated with estrogen develop an inability to sustain episodes of SWS and initiate PS episodes.

Light and electron microscopic observations on the cervical epithelium of the rabbit: II.

The endocervical epithelium of long-term ovariectomized rabbits treated for 1-10 days with 5 micrograms of estradiol benzoate every 12 hr has been studied by light and electron microscopy. In addition, morphometric data on ciliated and nonciliated cells of rabbits treated for 2, 6, and 10 days are compared to those on untreated ovariectomized, estrous, and ovulatory rabbits. The percentage of ciliated cells increases after ovariectomy to 76.3% and that of secretory cells decreases to 23.7% as compared to estrous controls. Treatment of ovariectomized rabbits with estradiol results in a gradual increase in ciliated and secretory cell area, height, and nuclear area. After 10 days of treatment, cell areas are significantly larger than those in the ovulatory or estrous controls; cell height and nuclear areas have returned to preovariectomized levels; and the percentages of ciliated and secretory cells have reached those of estrous levels. Estradiol stimulates mitotic division of secretory cells but affects ciliogenesis minimally. In ciliated cells, estradiol treatment results in a modest increase in polysomes and granular endoplasmic reticulum and in striking increases in the size of the Golgi complex and in the number of lipofuscin bodies as compared to those in the ovariectomized controls. In secretory cells, estradiol treatment brings about an increase in the numbers of polysomes, Golgi complexes, and cisternae of the granular endoplasmic reticulum, in the sizes of the nucleoli, and in the amount of euchromatin. Secretory granules appear in some cells after 2 days of estradiol stimulation and increase in number through 10 days of treatment. Perinuclear granules are more pleomorphic and heterogeneous in structure and more numerous in the 6- to 10-day-estradiol-treated than in ovulatory animals, and they may function as lysosomes degrading excess secretory product. Deep apical concavities of the secretory cells occur most often after 2 and 6 days of treatment.

Differential responsiveness of LH and prolactin to p-tyramine in male and female rats.

The effect of p-tyramine, a natural amine which is found in the rat brain in trace amounts, was evaluated for its capacity to influence LH and prolactin secretion in male and female rats under different hormonal conditions. p-Tyramine (40 mg/kg ip) was ineffective in modifying LH levels in either female or male rats which had been gonadectomized for 2 days, but if the animals were injected with 12.5 micrograms of estradiol benzoate (EB) on the day of castration, p-tyramine was able to release LH in female but not in male rats. To evaluate whether early androgenization of brain structures which control LH secretion was involved in the sexual difference observed, p-tyramine was tested in female androgenized rats (200 micrograms of testosterone propionate on the day of birth), and in male rats castrated at birth. The trace amine was ineffective in altering LH levels in both experimental models, even if rats were pretreated with EB as control females. On the other hand, p-tyramine inhibited prolactin secretion in male rats pretreated with EB, and not in similarly treated female rats. The present results suggest that p-tyramine may be involved not only in prolactin regulation as it has been previously shown, but also in LH control, and that the hormonal response to this amine is sexually differentiated in the rat.

The effect of estrogen on luteinizing hormone-releasing hormone binding sites in hypothalamic membranes.

The binding sites for [125I]LHRH were characterized in membranes from the hypthalamus and the effect of estrogen on the binding characteristics was studied in ovariectomized female rats. The radioligand, [125I]LHRH, was found to bind specifically to membranes from the hypothalamus at a maximal level, with an optimal temperature of 0 degrees C and a pH between 7 and 8. The binding was enhanced by NaCl at a concentration of 0.1-0.2 M. The specifically bound [125I]LHRH was only displaced by LHRH, but not by sodium iodide (NaI), bovine serum albumin and other hormones, such as thyrotropin-releasing hormone, bradykinin, oxytocin, prolactin, luteinizing hormone and growth hormone. The divalent metal ions, copper (Cu2+) and mercury (Hg2+), inhibited the specific binding of [125I]LHRH completely, whereas magnesium (Mg2+) and calcium (Ca2+) caused a decrease in binding. As revealed from Scatchard plot analysis, the binding sites for [125I]LHRH in the hypothalamus had a dissociation constant of 0.40 +/- 0.03 microM and the maximum number of binding sites was 98.55 +/- 4.34 pmol/mg protein. Treatment of female rates (ovariectomized for 3 weeks) with 4 micrograms of estradiol benzoate caused a statistically significant decrease in the maximal number of binding sites without any significant effect on the dissociation constant. However, the direct addition of estradiol hemisuccinate to the membrane preparations had no statistically significant effect on the specific binding of [125I]LHRH. The present study provides the evidence that estrogen decreases the density of binding sites for [125I]LHRH in the hypothalamus in vivo.

Effects of neonatal estrogenization on rat bone development: a histomorphometric study.

The effects of a single dose of 500 micrograms of estradiol benzoate, administered on the first day of life, on rat bone development have been histomorphometrically studied at 15 days of age. Estrogenized animals presented decreased total tibial length (16.55 +/- 0.50 vs. 17.84 +/- 0.73 mm, P less than 0.05) and increased thickness of the cartilage growth plate (528.92 +/- 13.30 vs. 382.77 +/- 37.85 micron, P less than 0.01). This increase was mostly due to the presence of a wider (P less than 0.01) layer of hypertrophic cartilage in the estrogenized rats than in control ones. It might be related to the decreased number of chondroclasts (0.20 +/- 0.01 vs. 0.36 +/- 0.06 mm-1, P less than 0.05) found in the resorption zone. Two metaphyseal zones have been considered. In the upper metaphyseal zone there was an increase in the surface density of the cartilaginous trabeculae (49.20 +/- 1.80 vs. 40.72 +/- 1.95 mm2/mm3, P less than 0.05), without changes in the volume density. It was related to the presence of thinner and more irregular trabeculae in the estrogenized animals. In the lower metaphyseal zone both the volume (0.19 +/- 0.01 vs. 0.14 +/- 0.01 mm3/mm3, P less than 0.01) and surface (34.83 +/- 3.01 vs. 26.52 +/- 2.46 mm2/mm3, P less than 0.05) densities of the osseous trabecular tissue were increased in estrogenized rats. No significant differences were found either in the number of osteocytes per area unit of osseous tissue or in the number of osteoclasts per unit length of trabecular osseous tissue.

Incorporation of amino acids into proteins of the hypothalamus of prepuberal female rats after estradiol treatment.

The arcuate nucleus-median eminence complex (AM) undergoes major structural and functional changes during normal puberty or if exposed to a pulse of estradiol in the prepuberal period. Those changes are expressed by increased synaptogenesis and by a drastic alteration in the feedback control of anterior pituitary gland hormone release. In this study we investigated the effects of estradiol benzoate (EB) on specific proteins in this hypothalamic area. Prepuberal, 25-day-old female rats were administered 10 micrograms of EB s.c. in oil or sesame oil vehicle. The animals were decapitated either 17 or 42 h after treatment. The brains were removed, blocked and serially sections at 300 micron using a Vibratome. The AM was dissected out and incubated for 6 h in a medium containing 35S-methionine and 35S-cysteine. Proteins from the AM were separated by two-dimensional gel electrophoresis, and the gels were exposed to X-ray film. The resulting autofluorographs were analyzed by scanning densitometry. The results show that the incorporation of labeled amino acids was increased in 10 proteins and decreased in 2 proteins in rats killed 17 h after EB. At 42 h after EB, 6 proteins showed an increased incorporation of amino acids and two proteins showed a decrease. Our results suggest that one or several of these proteins might be involved in the neuroendocrine and structural changes observed in the AM during puberty.

Possible role of alpha-2-noradrenergic receptors in modulation of sexual behavior in female guinea pigs.

These studies examine whether alpha 1-noradrenergic receptor stimulation alone is sufficient to facilitate lordosis behavior in ovariectomized, estrogen-primed female guinea pigs and to what extent alpha 2-noradrenergic receptors are involved in this steroid-dependent behavior. Neither of the alpha 1-agonists, phenylephrine or methoxamine, significantly facilitated lordosis in ovariectomized females primed with 10 micrograms of estradiol benzoate for 1 or 3 days. Animals exhibiting estrogen plus clonidine-facilitated lordosis showed a decrease in the behavior when given one of two alpha 2-antagonists (yohimbine or idazoxan). Idazoxan also attenuated lordosis in animals given estrogen plus progesterone. These findings, in combination with previous findings (that specific alpha 1-antagonists block lordosis), suggest that alpha 2-receptors, in addition to alpha 1-receptors play a role in modulation of lordosis behavior.

Differences among ovariectomized female rhesus macaques in the display of sexual behavior without and with estradiol treatment.

Ovariectomized, estrogen-primed, adult female rhesus macaques were preselected for the display of high (HLP) and low (LLP) levels of sexual performance. Eight sexually vigorous adult males were selected as partners. For 13 consecutive days each month, females received 0, 2.5, 5.0, and 10.0 micrograms of estradiol benzoate (EB) and were tested on Days 12 and 13 of injection. Blood samples were taken before and on the last day of each of the four injection series, and serum levels of estradiol, progesterone, and testosterone were determined with a radioimmunoassay. The HLP females (n = 5) displayed higher levels of receptivity and proceptivity and received more mounts, intromissions, and ejaculations when tested without EB treatment than LLP females (n = 5) did when they were tested with 10.0 micrograms of EB. Female receptivity, proceptivity, and attractiveness cannot be explained by estrogen action alone. The effectiveness of estrogen is limited by the somatic characteristics of the individual on which it acts.

Kainic acid lesioning of the preoptic area alters positive feedback of estrogen in prepubertal female rats.

Stereotaxic infusion of kainic acid (KA) was performed to induce intrinsic neural lesions of the preoptic area (POA) in 25-day-old female rats. After KA infusion, rats in Experiment 1 received 10 micrograms of estradiol benzoate (EB) administered subcutaneously to assess positive feedback of EB on release of luteinizing hormone (LH) from the pituitary gland. Rats were perfused for light microscopic (LM) or electron microscopic (EM) evaluation of the lesion site. Rats of Experiment 2 were allowed to develop until the appearance of vaginal opening (VO) after which time vaginal lavages were taken to monitor the cyclicity of the vaginal epithelium. At 50 days of age, the right ovary from each rat was removed, trimmed of fat, and weighed. At 60 days of age, the remaining ovary was removed to assess compensatory ovarian hypertrophy (COH). In Experiment 3, we investigated the effects of POA/KA-infusion on sexual behavior. Sex behavior tests were conducted at 48 h after EB during the dark phase of the light cycle. In Experiment 1, all the control and saline-infused rats exhibited the expected rise of plasma LH two days after estrogen injection while the POA/KA-infusion abolished the positive feedback effect of EB on LH release. Ultrastructural examination of the lesion site revealed that neurons were undergoing acute degeneration while axons and afferent terminals seen in the same fields of analysis were morphologically intact. Preoptic area/KA lesions caused a marked delay in the appearance of VO. Duration of this temporal delay in POA/KA-lesioned rats was approximately 4 days, or one vaginal cycle. The lesioned animals showed normal compensatory hypertrophy after unilateral ovariectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroxine treatment reduces the anorectic effect of estradiol in rats.

In order to examine a possible interaction between thyroxine and estradiol in the control of feeding, 14 ovariectomized adult female rats were given daily injections of 9.8 micrograms/100 g of body weight of 1-thyroxine (T). Another 14 rats received 0.15 ml of saline (S) subcutaneously each day, and food intake was measured for both groups daily. After 15 days of treatment, 8 rats from each group were also given a single injection of 6 micrograms of estradiol benzoate (EB), and the remaining 6 rats of each group received peanut oil vehicle. It was found that T-treated rats showed a significantly smaller drop in food intake after EB than did S-treated rats. This thyroxine-induced decrease in responsiveness to EB did not appear due to any changes in body weight per se but may be related to effects of thyroxine on general metabolism.

Effects of body weight, adrenal status, and estrogen priming on hypothalamic progestin receptors in male and female rats

Some laboratories have reported sex differences in the effect of estrogen priming on neural progestin receptor concentration, whereas others find no such differences. The present studies sought to identify experimental variables which might differentially influence the measurable level of hypothalamic cytosol progestin receptors in adult male and female rats. The influence of three variables, body weight, adrenal status, and estrogen priming regimen, was evaluated. Treatment with low doses of estrogen (2 or 8 micrograms of estradiol benzoate (EB) 48 hr before sacrifice) was slightly but not significantly more effective in elevating hypothalamic progestin receptor content in age-matched females than in males despite the 40% greater body weights of males. When the same doses of EB were administered per 200 gm of body weight to animals with and without adrenal glands, both basal and estrogen-induced levels of hypothalamic progestin receptor were significantly higher in adrenalectomized/gonadectomized rats than in rats which were gonadectomized only, regardless of sex. There was no significant effect of sex or any interaction between sex, adrenal status, or estrogen priming dose. The only significant sex difference in brain progestin receptors occurred when weight-matched males and females received multiple injections of higher priming doses of estrogen (three daily injections of 10 micrograms of EB). Under these conditions, females showed up to 2-fold higher levels of hypothalamic progestin receptors than males, regardless of adrenal status. These data suggest that sex differences may exist in the neural progestin receptor systems of male and female rats, but the relationship of these differences to sex differences in neuroendocrine function or behavior is not clear.