Antagonistic effects of estradiol dipropionate and progesterone on the histology of the vagina and uterus of the mouse

Administration of estradiol dipropionate (20 micrograms/day; 7 days) to ovariectomized mice caused heavy epithelial proliferation and intense cornification in the vagina and cellular as well as glandular proliferation in uterine tissues. Endometrial hypertrophy with cystlike appearance of uterine glands was seen in response to a long-term (14 days) administration of estradiol dipropionate. Daily injection of progesterone (2 mg; 7 days) to ovariectomized mice resulted in desquamating mucosa, without any trace of vaginal cornification, and the presence of dense uterine connective tissue in the stromal region with typical uterine glands. However, treatment of estradiol depropionate in combination with progesterone at 1:100 dose ratio for 7 days produced vaginal histology similar to that in proestrus and uterine histology equivalent to the ovariectomized condition. The results revealed that progesterone antagonized the estrogenic effects and also that estradiol dipropionate antagonized the effects of progesterone. The effects of the two female sex steroids (estradiol dipropionate and progesterone) in vivo appeared to be more potent in the uterus than in the vagina.     

Sex hormone regulation of anti-bacterial activity in rat uterine secretions and apical release of anti-bacterial factor(s) by uterine epithelial cells in culture

In mature female rats, sex hormones regulate the reproductive (estrous) cycle to optimize mating and fertility. During the part of the estrous cycle when mating occurs, and when estrogen is the dominant sex hormone, the uterus is susceptible to infection with bacteria that can be deleterious for survival and fertility. The present study investigated whether sex hormones regulate innate immunity in the female reproductive tract by affecting the secretion of an anti-bacterial factor(s) in the rat uterus. Uterine fluids from intact rats at the proestrous stage of the estrous cycle significantly inhibited Staphylococcus aureus growth. When ovariectomized rats were treated with estradiol, anti-bacterial activity against both S. aureus and Escherichia coli increased in uterine secretions with hormone treatment. In contrast, rats injected with either progesterone and estradiol or progesterone alone displayed no bactericidal activity indicating that progesterone reversed the stimulatory effect of estradiol on anti-bacterial activity. In other studies, isolated uterine epithelial cells from intact animals were grown to confluence and high transepithelial resistance on cell inserts. Analysis of apical secretions indicated that a soluble factor(s) is released by polarized epithelial cells which inhibits bacterial growth. These results demonstrate that sex hormones influence the presence of a broad-spectrum bactericidal factor(s) in luminal secretions of the rat uterus. Further these studies suggest that epithelial cells which line the uterine lumen are a primary source of anti-bacterial activity.     

Actions of progesterone on uterine immunosuppression and endometrial gland development in the uterine gland knockout (UGKO) ewe

In ewes, the uterine gland knockout (UGKO) phenotype is caused by neonatal exposure to norgestomet to arrest uterine gland development and produce an adult which has a uterus characterized by the lack of endometrial glands. Since endometrial glands in the sheep produce the lymphocyte-inhibitory protein, ovine uterine serpin (OvUS), an experiment was conducted with ewes of the UGKO phenotype to evaluate whether the inhibitory actions of progesterone on tissue rejection responses in utero are dependent upon the presence of endometrial glands. Control and UGKO ewes were ovariectomized and subsequently treated with either 100 mg/day progesterone or corn oil vehicle for 30 days. An autograft and allograft of skin were then placed in each uterine lumen and treatments were continued for an additional 30 days before grafts were examined for survival. All autografts survived and had a healthy appearance after histological analysis. Allografts were generally rejected in ewes treated with vehicle but were present for hormone-treated ewes, regardless of uterine phenotype. Analysis of the histoarchitecture and protein synthetic capacity of the uterus revealed that progesterone induced differentiation of endometrial glands and synthesis and secretion of OvUS in UGKO ewes. The UGKO ewes had reduced density of CD45R+ lymphocytes in the endometrial epithelium and there was a tendency for progesterone to reduce this effect in luminal epithelium. Taken together, results confirm the actions of progesterone to inhibit graft rejection response in utero. Responses of UGKO ewes to progesterone indicate that the hormone can induce de novo development and differentiation of endometrial glands, at least when skin grafts are in the uterus.     

Influence of sex hormones on prostaglandin dehydrogenase activity in the rat uterus

The present experiments report the effects of estradiol or of progesterone on the activity of 15-prostaglandin-dehydrogenase (PGDH) in the uterus of spayed rats. When the substrate was PGF2 alpha the treatment with progesterone (4 mg X day-1, two days) or with estradiol-17-beta (0.5 ug + 1 ug) did not show any effect on the activity of the enzyme. On the contrary, uteri from ovariectomized rats injected with a higher dose of estradiol-17-beta (0.5 ug + 50 ug) exhibited a significant increment. When the substrate was PGE2, progesterone failed again to modify the enzyme activity, whereas estradiol, both at a low and at a high doses, enhanced significantly the uterine PGDH activity. The possibility of two different PGDHs for each PG and the role of estradiol in enhancing PGE2 catabolism into 15-keto-PGE2 as a mechanism subserving the effect of estrogens on the output of this PG in the rat uterus, are discussed.     

Effects of estradiol, progesterone, and norethisterone on regional concentrations of galanin in the rat brain.

Concentrations of immunoreactive galanin were compared in eight gross brain regions of ovariectomized female rats treated with either estradiol, estradiol + progesterone, estradiol + norethisterone, or placebo. Higher concentrations with estradiol treatment compared with placebo were found in the pituitary (357%), frontal cortex (162%), occipital cortex (174%), hippocampus (170%), and median eminence (202%). A more profound difference with addition of progesterone or norethisterone was seen in the pituitary (529% and 467%, respectively). Sex steroids, particularly estradiol, modulate galanin concentrations not only in reproductive, but also in nonreproductive, brain regions.     

Regulation of myometrial beta 2-adrenergic receptors by progesterone and estradiol-17 beta in late pregnant rats

Rat myometrium exhibited a marked decrease in the concentration of beta 2-adrenergic receptors immediately before parturition, i.e., in the last 6 h of pregnancy. This phenomenon continued until the withdrawal of myometrial progesterone (-94% from Day 18 of pregnancy to term) and coincided with the sharp increase (+200%) of the myometrial concentration of estradiol. A linear positive correlation was found (r2 = 0.645) between the concentration of beta 2-adrenergic receptors and the log ratio of myometrial concentration of progesterone/myometrial concentration of estradiol (P/E2), suggesting a modulation of beta 2-adrenergic receptors by steroids. In rats with estrogen-dominated uteri (intact of ovariectomized late pregnant rats injected with estradiol), there was no change either in concentration or affinity of beta 2-adrenergic receptors relative to untreated control pregnant rats. In contrast, rats with progesterone-dominated uteri (intact or ovariectomized late pregnant rats treated with progesterone or ovariectomized rats) have an increased number of beta 2-adrenergic receptors, with a decreased affinity of these receptors compared to untreated control pregnant rats or to estrogen-treated rats. These results suggest that progesterone regulates the number of beta 2-adrenergic receptors in myometrium of late pregnant rats. The mechanisms by which progesterone exerts this regulation remains to be elucidated.     

Steroid-induced proteins secreted by the uterus of the guinea pig.

This study was conducted to identify proteins synthesized and secreted de novo by the guinea pig uterus. Uterine samples were obtained from cycling, late-pregnant as well as ovariectomized and steroid-treated guinea pigs and cultured with either L-[3H]leucine or L-[35S]methionine. Two-dimensional SDS-PAGE of culture medium followed by fluorography was used to determine proteins synthesized and secreted de novo during a 24-h incubation period. Two complexes of estradiol-stimulated proteins (ESP) were detected. Each complex was composed of 5-7 unique proteins with slightly different isoelectric points. The higher molecular-weight complex had a molecular weight of 65,000-60,000 and an isoelectric point range of 5.2-6.1. The lower molecular-weight complex had a molecular weight of 60,000-55,000 and a similar range of isoelectric points. The two complexes of ESP were not observed in medium of explants from animals that received placebos, were late-pregnant, or were treated with progesterone only. Progesterone administered in combination with estradiol enhanced production of both complexes of ESP to similar degrees. Neither complex of ESP was secreted by the explant culture in the presence of tunicamycin, suggesting that the proteins are glycosylated. These findings demonstrate that the uterus of the guinea pig produces two unique complexes of proteins in response to estradiol stimulation, and all results are consistent with the hypothesis that ESP are contained in the carbohydrate-rich secretory granules of endometrial gland cells.     

Expression of peptidylarginine deiminase in the uterine epithelial cells of mouse is dependent on estrogen.

The effects of the steroid hormones estrogen and progesterone on peptidylarginine deiminase protein-L-arginine iminohydrolase, EC 3.5.3.15) levels in adult ovariectomized mouse uterus were studied. The amount of the enzyme in the uterus was considerably diminished by ovariectomy. When the mice were injected with a variety of estrogenic compounds, 17 beta-estradiol-3-benzoate, which was the most potent stimulator of uterine cell proliferation among the estrogens tested, dramatically elevated the enzyme formation of the uterus in a dose- and time-dependent fashion. Results of immunohistochemistry with the antiserum against mouse peptidylarginine deiminase demonstrated that the induction of the enzyme by the estradiol exclusively occurred at the luminal and glandular epithelia, corresponding with the previous findings in the normal estrous cycle. Furthermore, administration of the estradiol significantly increased the content of mRNA coding for peptidylarginine deiminase in uterus, indicating the evidence of regulation in pretranslation. On the other hand, progesterone alone did not restore the enzyme level of the ovariectomized mouse, but moderated the action of estrogen when given in concert with estrogen. Thus, the expression of peptidylarginine deiminase in luminal and glandular epithelia of mouse uterus is controlled by the amount of the steroid hormones estrogen and progesterone.     

Cyclic estradiol treatment normalizes body weight and restores physiological patterns of spontaneous feeding and sexual receptivity in ovariectomized rats

Hypothalamic-pituitary-gonadal axis function strongly influences feeding and body weight in cycling females in many species. To test the sufficiency of cyclic variations in plasma estradiol to reproduce normal patterns of spontaneous feeding, food intake, and body weight, ovariectomized Long-Evans rats were subcutaneously injected every fourth day with 2 microg estradiol benzoate or with the oil vehicle alone. Cyclic estradiol treatment completely normalized the trajectory of body weight gain and total food intake through seven treatment cycles. The hyperphagia of ovariectomized rats was expressed as an increase in spontaneous meal size. Meal frequency decreased, but not enough to compensate for the increase in meal size. Estradiol treatment normalized both parameters. In addition, cyclic estradiol treatment produced a further phasic decrease in meal size (and increase in meal frequency) and a decrease in food intake during the second night after injection. This phasic change is similar to the feeding changes occurring during estrus in intact rats. Sexual receptivity was measured during the eighth estradiol treatment cycle, 4 h after injection of 0.5 mg progesterone. Lordosis scores at the time of the treatment cycle modeling estrus were maximal, and scores at the time modeling diestrus were slightly increased over those of rats that did not receive estradiol. Finally, plasma estradiol levels, measured during the ninth treatment cycle, revealed a near-normal cyclic pattern of plasma estradiol levels. These results provide the first demonstration that the induction of a cyclic, near-physiological pattern of plasma estradiol is sufficient to maintain normal levels of body weight, spontaneous feeding patterns, total food intake, and (together with progesterone) sexual receptivity in ovariectomized rats.     

Regulation by Gonadal Steroids of Estrogen and Progesterone Receptors Along the Reproductive Tract in Female Lambs

The regulation of estrogen and progesterone receptor (ER, PR) expression by estradiol (E2) and progesterone (P4) in the oviduct, uterus and cervix of female lambs was studied. The animals received three intramuscular injections of E2, P4 or vehicle with an interval of 24 h and they were slaugthered 24 h after the third injection. Determinations of ER and PR were performed by binding assays and mRNAs of ERα and PR by solution hybridization. High levels of ER and PR in both cervix and oviduct were found in the female lamb, differing from other mammalian species. No significant effects by either E2 or P4 treatment on ER and PR levels in the cervix and oviduct could be observed. E2 treatment increased the mRNA levels of ERa and PR more than 3-fold in the cervix, while P4 treatment increased the mRNA levels of ERa and PR in the uterus. The results show differential effects of gonadal steroids on sex steroid receptor expression along the reproductive tract in female lambs, suggesting that steroid target tissues can modulate responses to the same circulating levels of steroid hormones.     

Ultrastructure of the uterus in an ovariectomized gecko (Hemidactylus turcicus) after administration of exogenous estradiol

The uterus of an oviparous gecko, Hemidactylus turcicus, was analysed after ovariectomized females underwent a period of treatment (up to 14 days) with exogenous estradiol. Analysis focused on the uterine mucosa, which is made up of an epithelial layer and an underlying lamina propria containing the shell glands. These tissues are thought to be responsible for secretion of the eggshell components and were thus chosen for analysis using transmission electron microscopy. In ovariectomized females, the epithelial layer was low and cuboidal with minimal/no differentiation or secretory activity. Treatment with exogenous estradiol resulted in a significant increase in cell height associated with gradual differentiation of the epithelium. Development of non-ciliated cells included production of secretory granules (low electron density) at the apical cell surface. The shell glands showed less obvious changes over the course of treatment. Shell glands contained two cell types: dark cells with darkly staining nuclei and organelles, and light cells with very indistinct nuclei and organelles, except for prominent rough endoplasmic reticulum and free ribosomes. This study provides results consistent with published light microscopy studies for other reptiles and additionally provides ultrastructural details of reptilian uterine development not previously available.     

Tamoxifen decreases the estradiol induced progesterone receptors by interfering with nuclear estrogen receptor accumulation

The retention time of the estrogen receptor in the nucleus of target cells after antiestrogen treatment has been shown to be longer than after estradiol. This paper describes the accumulation of nuclear estrogen receptors and the obtention of estrogenic responses (i.e. synthesis of cytosolic progesterone receptors and DNA) in the rat uterus after tamoxifen treatment in the presence or absence of estradiol. One-week ovariectomized adult rats were implanted with a silicone elastomer capsule containing corn oil or 25 micrograms estradiol/capsule (0 h). 48 h after implantation rats were injected with corn oil or 2 mg tamoxifen/kg and decapitated at 72, 96 or 120 h after implantation. In parallel experiments the implants were removed just before the injections of tamoxifen or oil. Tamoxifen injected into rats implanted with oil increased both the occupied nuclear receptors and the progesterone receptors at 96 h. In rats implanted with estradiol, tamoxifen did not increase the occupied nuclear receptors and decreased the levels of progesterone receptor and DNA at 96 h. In rats whose estradiol implants were removed at 48 h tamoxifen did not change the level of occupied nuclear receptors at 72 h but it increased them abruptly at 96 and 120 h. In these rats progesterone receptors decreased at 72 h but they increased at 96 and 120 h, and DNA decreased at 120 h to a lower level than before implantation. The results suggest that when estradiol is acting, tamoxifen is not able to increase the level of occupied estrogen receptor and it acts as an antiestrogen by decreasing the high level of progesterone receptors previously induced by estradiol. When estradiol is not acting tamoxifen behaves as a partial estrogen agonist by inducing progesterone receptors. However, the antiestrogenic action of tamoxifen on the rat uterus DNA does not seem to be affected by estradiol.     

Evidence of sex hormone binding globulin binding sites in the medial preoptic area and hypothalamus.

We have demonstrated a high density of both radiolabeled progesterone and estradiol conjugated to bovine serum albumin binding sites in the medial preoptic area and hypothalamus. Infusions of sex hormone binding globulin into the medial preoptic area of rats increased their female sexual receptivity similarly to the effect of estradiol conjugated to bovine serum albumin, suggesting sex hormone binding globulin acts at binding sites for estradiol conjugated to bovine serum albumin. In this study sex hormone binding globulin was used to displace radiolabeled progesterone conjugated to bovine serum albumin from plasma membrane fractions from the medial preoptic area-anterior hypothalamus and medial basal hypothalamus of ovariectomized rats injected with either 5 microg estradiol benzoate or sesame oil vehicle. We found that sex hormone binding displaced radiolabeled progesterone conjugated to bovine serum albumin in both areas and that in vivo estradiol treatment greatly increased the relative displacement by sex hormone binding globulin in the medial preoptic area-anterior hypothalamus. We interpret these data as indicating the presence of sex hormone binding globulin receptors in brain plasma membranes and further suggest that endogenous steroid conditions may alter these receptors.     

A physiological dose of estradiol with progesterone affects striatum biogenic amines

The acute effect of estradiol and progesterone on dopamine and serotonin metabolism in rat striatum was studied. One subcutaneous injection of 17 beta-estradiol (300 ng) and progesterone (150 micrograms) into intact male rats increased plasma levels of these steroids, while testosterone, corticosterone, and estrone remained unchanged. Dehydroepiandrosterone, androstane-3 beta, 17 beta-diol and dihydrotestosterone remained undetectably low. Prolactin decreased and androstane-3 alpha, 17 beta-diol, and 17-OH progesterone increased, but less than estradiol and progesterone. Peak levels of striatal dopamine, dihydroxyphenylacetic acid, and homovanillic acid were observed 15-45 min after steroid injection with a return to control values after 45-60 min, while serotonin and 5-hydroxyindoleacetic acid levels were slightly decreased. An injection of estradiol (70 ng) with progesterone (70 micrograms) to ovariectomized female rats left plasma prolactin levels unchanged, while striatum dopamine and serotonin as well as their metabolite concentrations peaked 15-60 min after steroid injection and returned to control values after 45-75 min. To allow for a better comparison of the action of these steroids, the effect of estradiol or progesterone alone and in combination on the brain of ovariectomized rats was compared in the same experiment. A similar increase in metabolites of dopamine levels was observed after these steroids alone or in combination, while dopamine levels were increased only after progesterone alone or in combination with estradiol. An injection of estradiol or progesterone to ovariectomized rats led to peak steroid concentrations at approximately the same time in the brain and plasma. In addition, plasma and brain steroid levels were significantly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Appearance of beta-hexosaminidase and other lysosomal-like enzymes in the uterine lumen of gilts, ewes and mares in response to progesterone and oestrogens

In one experiment, ovariectomized gilts were treated with corn oil (vehicle), progesterone, oestradiol-17 beta or both steroids. While oestradiol treatment did not stimulate enzyme activity in uterine flushings relative to vehicle-treated animals, gilts treated with progesterone had elevated amounts of all enzymes measured. Progesterone was less effective when co-administered with oestradiol-17 beta. Enzymes were not equally stimulated by progesterone. For example, there was a 909-fold increase in acid phosphatase activity in uterine flushings and a 304-fold increase in beta-N-acetylglucosaminidase, but only a 10-fold increase in beta-glucosidase. Endometrial explants from gilts synthesized and secreted radiolabelled beta-N-acetylglucosaminidase, suggesting that at least some lysosomal enzymes enter the uterus through secretory processes. In other experiments, changes in beta-N-acetyglucosaminidase in uterine fluids of mares and ewes treated with hormonal regimens similar to those given to the gilts were evaluated. Treatment with the combination of progesterone and oestrogen stimulated accumulation of the enzyme relative to that in vehicle-treated animals. The biochemical properties of porcine beta-N-acetylglucosaminidase were examined in detail. Properties of the uterine enzyme were similar to reported values for lysosomal hexosaminidase. These included molecular weight (82 000-89 000), pH optimum (pH 4.4), presence of two isomers (isoelectric points of 5.5 and 8.0) and ability to hydrolyse substrates for glucosaminidase and galactosaminidase. We conclude that steroids induce the accumulation of lysosomal enzymes in the uterine lumen. The degree of stimulation differed between enzymes, suggesting that those enzymes stimulated to the greatest extent may play an important role in pregnancy.     

Ovarian hormones inhibit the release of prostacyclin-like material from isolated rat uterus

The influence of sex steroids on the production of prostacyclin (PGI₂) like material by the isolated rat uterus incubated in a buffer medium was explored by monitoring its ability to inhibit ADP-induced platelet aggregation. Chopped uterine strips from rats in natural estrus can generate an unstable substance that inhibits platelet aggregation and suggest to be prostacyclin. This capacity was significantly enhanced in preparations from spayed animals. The injection of 17-beta estradiol; progesterone or both diminished the production of the prostacyclin-like material by the uterus from ovariectomized rats. The already existing notion that ovarian steroids are able to regulate the synthesis of stable prostaglandins is discussed together with the present results suggesting in addition a depressive effect of sex hormones on the uterine PGI₂ synthetase system.     

Effect of estradiol and progesterone on oviductal LH-receptors and LH-dependent relaxation of the porcine oviduct

We have previously shown that the porcine oviduct possesses immunoreactive and functional LH receptors and that LH causes relaxation of the oviduct, especially during the periovulatory stage of estrous cycle. The current studies were undertaken to investigate the effects of estradiol and progesterone on LH receptor protein and LH-stimulated motility of the oviduct in steroid-primed ovariectomized gilts. Twenty-one cross-bred gilts were ovariectomized at 6 m.o. of age. Four weeks later gilts received daily intramuscular injection of either 2 mL corn oil (control n = 4), estradiol benzoate (EB) 1.5 mg (n = 6), progesterone 50 mg (n = 5), or 1.5 mg EB plus 50 mg progesterone (n = 6) for 4 consecutive days. The gilts were slaughtered on Day 5 after the first injection of steroids or vehicle. Rings of isthmus and ampulla were collected from each oviduct and placed in a tissue chamber perfused with Kreb's solution for 60 min. The mechanical activity was recorded for 30 min after LH treatment. Immunoreactivity of LHR in the Fallopian tube sections were detected in the epithelium of the tubal mucosa, smooth muscle cells and the blood vessel endothelium. Western blotting showed that porcine oviducts contain 75, 48 and 45 kDa immunoreactive LH receptor proteins, like the corpus luteum (CL). The lowest receptor expression was found in controls and in gilts treated with estradiol or progesterone. Combined treatment with estradiol and progesterone resulted in a significant increase of LH receptor protein concentrations when compared with control animals. In vitro LH treatment affected oviduct contractility of combined estradiol and progesterone treated gilts but not the oviduct of the remaining groups. It also caused a decrease in amplitude, frequency and areas under the curve (AUC) of ampulla (P < 0.05) and the amplitude and AUC of isthmus (P < 0.001) in combined estradiol and progesterone-primed gilts. These results indicate that estradiol and progesterone together, but not separately, increase LH receptor protein in the porcine oviduct and that combined estradiol and progesterone priming is necessary for LH-induced relaxation of the porcine oviduct.     

Female sperm storage in reptiles.

Internal fertilization and oviparity most likely are symplesiomorphies for modern reptiles, and viviparity has evolved independently numerous times in Sauria and Serpentes. Oviducal sperm storage is known in females of all taxa except Amphisbaenia. However, in Rhynchocephalia and Crocodilia, sperm storage is poorly studied, and specialized sperm storage tubules (Ssts) are unknown. We use the molecular phylogenetic hypothesis [(Chelonia+Archosauria) (Squamata)] to trace evolution of sperm storage characters. Ssts arose independently in Chelonia and Squamata. Turtles possess albumen-secreting glands in the anterior half of the oviduct (the tuba or isthmus), and the most distal of these glands also serve as Ssts; in addition, some turtles possess Ssts in the adjacent segment of the oviduct, the uterus. Squamates lack albumen-secreting glands, and the ancestral state is possession of Ssts in the posterior infundibulum (uterine tube). Secondarily, iguanids have evolved vaginal Ssts. In this paper, we present the first ultrastructural observations on vaginal Ssts in lizards, using Anolis sagrei (Polychrotidae). Proximally, the neck of these simple tubular glands continues the alternation of ciliated and secretory cells lining the lumen of the vagina. However, the epithelial cells of the distal sperm storage area are neither secretory nor ciliated. The Ssts of Anolis are more similar to those of birds more than to infundibular receptacles in snakes and lizards.     

Oviductal epithelium of the baboon: hormonal control and the immuno-gold localization of oviduct-specific glycoproteins

Oviducts were obtained from a series of cycling and ovariectomized steroid-treated baboons. The lining epithelium of the ampulla and isthmus was analyzed by light and electron microscopy. Both morphological and cytomorphometric analyses revealed that the morphological and functional state of the oviductal epithelium in the baboon is controlled by the ovarian steroids. Additionally, a clear cephalocaudal steroid-responsive gradient was observed when the data from the ampulla and isthmus of the same animal were compared. Within the ampulla, estradiol induced hypertrophy, hyperplasia, ciliogenesis, and secretory activity, whereas adding progesterone to the treatment regimen (+/- estradiol) resulted in atrophy, deciliation, apoptosis, and loss of the secretory activity. These cyclic processes were less evident in the isthmus. We also used an indirect electron microscopic immunogold technique and a previously characterized polyclonal antibody to determine the localization of oviduct-specific glycoproteins. These glycoproteins were present in every secretory granule observed, regardless of oviduct region, electron density, or size of the secretory granule. In summary, our data show that 1) estradiol induces and maintains the mature epithelium of the baboon oviduct, 2) steroid withdrawal or the administration of progesterone causes regression of the epithelium, and 3) the previously identified estradiol-dependent oviduct-specific glycoproteins are synthesized within and released from the secretory epithelial cells.