Synchronization of estrus in post-partum mares with progesterone and estradiol 17β

Thirty-six mares which foaled over a 10-day period were given 1 to 10 daily intramuscular injections of a combination of 150 mg. progesterone and 10 mg. estradiol 17β. The first injection was given within 18 hours after parturition. Because individual mares foaled on different dates during the 10 day period, commencement of treatment varied, but treatment for all mares ceased on the same day. Teasing and breeding began seven days after the final treatment. The mares were teased daily for 10 days and artifically inseminated every second day until ovulation occurred. The mean interval from the end of treatment to beginning of estrus was 9.4 days (range 7 to 14) and 33 of 26 mares (94.7%) ovulated 10 to 16 days after the final treatment. Both estrus and ovulation were effectively synchronized, resulting in a first estrus pregnancy rate of 80.6% (29 of 36).     

Testicular in vitro conversion of progesterone to testosterone and androstenedione in 17α-hydroxylase deficiency

Incubations of [³H]-progesterone with testicular tissue obtained from a new case of male with 17α-hydroxylase deficiency were performed. The per cent conversion to androstenedione and testosterone was virtually absent when compared to that obtained from an identical incubation performed using testicular tissue from a normal male with cryptochordism. The findings provide an in vitro evidence in support of the existence of 17α-hydroxylase testicular defect in this disorder.     

Autonomic innervation and plasma estradiol-17β and progesterone levels in rats with subcutaneous ovarian autografts

Summary Ovaries were removed from female rats and immediately autografted into a subcutaneous pouch in the flank in order to quantitate the relationship of graft re-innervation, steroid secretion and vaginal smear pattern. Animals were killed at three time periods: three days after grafting, on the first day a cornified vaginal smear appeared and at the first metestrus. In addition, control animals were killed at metestrus. Plasma samples were obtained from all rats and analyzed for estradiol-17 and progesterone concentration by radioimmunoassay.At the first day of vaginal cornification after grafting, plasma estradiol-17 (45.8±4.0 pg/ml) was elevated in comparison to controls at metestrus (24.0±2.6 pg/ml), but plasma progesterone (21.5±4.0 ng/ml) was not different (30.6±1.7 ng/ml). Subsequently, at the first metestrus following grafting, plasma estradiol-17 (23.0±3.5 pg/ml) was comparable to control values. In contrast, progesterone was decreased (17.5±1.9 ng/ml). A definite correlation was detected between the vaginal smear and plasma levels of steroid hormones in the castrated female rat with subcutaneous ovarian autografts.Histochemical techniques were used to study the adrenergic and cholinergic innervations of grafts three days after grafting, at the first day of vaginal cornification, and at the first metestrus. No correlation was shown between density of adrenergic or cholinergic innervation and plasma levels of estradiol-17 and progesterone or onset of a cycling vaginal smear.Supported in part by USPHS Grant T01-DE00241-04The authors wish to thank J. Canale, S. Hemelt, E. Schwartz and J. Skaggs for their technical and secretarial assistance. Anti-estradiol-17 antibody was obtained from Dr. I.H. Thorneycroft, University of Southern California School of Medicine, and anti-progesterone antibody from Dr. D. Tulchinsky, Harvard Medical Center     

Serum progesterone concentrations,follicular development and time of ovulation using a new progesterone releasing device (DICO®) in sheep

Four experiments were conducted to evaluate the effectiveness of a new controlled drug releasing device containing 0.3 g progesterone (DICO^®) on ovarian control in sheep. In experiment 1, serum progesterone concentrations induced by a 14 days treatment of DICO^® (n = 9) and CIDR-G^® (n = 9) were compared in ovariectomized ewes. Both devices induced similar responses and no differences were recorded. In experiment 2, the onset of oestrus and the time of ovulation obtained after 14 days treatment with DICO^® (n = 8) and CIDR-G^® (n = 7) were compared in cyclic ewes. Both devices induced oestrus and ovulation in all of the ewes. The onset of oestrus (34.5 ± 2.8 and 30.0 ± 7.7 h), the time of ovulation (60.0 ± 9.1 and 54.9 ± 6.4 h), the ovulation rate (1.3 ± 0.5 and 1.4 ± 0.5), the follicular diameter at ovulation (7.0 ± 0.8 and 7.3 ± 1.1 mm), and the lifespan of the ovulatory follicles (8.6 ± 2.2 and 10.0 ± 2.9 days) were similar for the DICO^® and CIDR-G^® devices, respectively. In Experiment 3, the re-utilization of DICO^® devices inserted for 6 days (i.e. short-term protocol) was evaluated in ovariectomized ewes. The females received a re-used (previously used for 6 days; n = 11) or a new DICO^® (n = 11) for a period of 6 days. The re-used DICO^® devices induced a lower serum progesterone concentration than the new devices (P < 0.05). However, the re-used DICO^® device maintained serum progesterone concentrations above 7.1 nmol/L (i.e. >2 ng/ml) throughout treatment. In Experiment 4, the administration of eCG treatment at DICO^® withdrawal was evaluated in cyclic ewes. The short-term protocol using DICO^® devices for 6 days was applied with (n = 8) or without (n = 7) 300 IU eCG at the time of device withdrawal. The administration of eCG advanced ovarian follicular development, synchronizing the onset of oestrus at 36 h and the time of ovulation at 60 h from device withdrawal. In conclusion, data from these experiments show the use of DICO^® or CIDR-G^® devices containing 0.3 g of progesterone to have a similar efficiency in controlling serum progesterone concentrations, follicular development and the time of ovulation in sheep. The re-use of the devices, associated with the short-term protocol for 6 days is possible, although further studies on induced fertility rates are warranted.     

Is progesterone a pre-hormone in the CNS?

In this paper, experimental evidences have been presented indicating that progesterone per se appears to be a powerful modulatory steroid of presynaptic striatal dopaminergic terminals of the central nervous system of the rat. This effect of the progesterone signal is concentration as well as infusion mode dependent. Low pulsatile doses of the steroid positively modulate the mechanism by which dopamine terminals respond to amphetamine stimulation and increase tissue dopamine concentration. Whereas, continuous and/or high doses of this steroid negatively modulate the response of the dopamine terminals to amphetamine stimulation and decreases tissue dopamine concentration. This effects occurs through a membrane mediated mechanism either upon the dopamine neuron directly and/or upon an interneuron. Pregnanolone a 5- beta-3 beta-metabolite of progesterone known to activate the hypothalamic LHRH neural apparatus at the level of the hypothalamus of ovariectomized estrogen primed rats in both in vitro as well as in vivo preparations was completely ineffective at the level of the corpus striatum of similar animal preparations. Therefore, it is reasonable to assume that site specific mechanisms exist within the central nervous system which may control differentially the final action of progesterone. In the hypothalamus, pregnanolone appears to be the final signal for its action on the LHRH neural apparatus, whereas in the corpus striatum, the steroid per se, and dependent on the modality and/or the strength of the signal can either directly or indirectly up-regulate (stimulatory component) or down-regulate (inhibitory component) the activity of striatal dopaminergic terminals.     

Efficiency of superovulation and in vivo embryo production in eFSH-treated donor mares after estrus synchronization with progesterone and estradiol-17β

Reliable methods of regulating estrus and stimulating superovulations in equine embryo transfer programs are desirable. Our objectives were to investigate the efficacy of a progesterone and estradiol-17β (P&E) estrus synchronization regimen in mares with and without subsequent equine follicle-stimulating hormone (eFSH) treatment and to examine the effects of eFSH on folliculogenesis and embryo production. Cycling mares were treated with P&E daily for 10 d. On the final P&E treatment day, prostaglandin F_2α was administered, and mares were randomly assigned to one of two treatment groups (n = 20 mares/group). In both groups, mares were examined daily by transrectal ultrasonography. In the eFSH group, twice-daily eFSH treatments were initiated at follicle diameter 20 to 25 mm and ceased at follicle ≥35 mm; human chorionic gonadotrophin (hCG) was administered after 36 h. In the control group, eFSH treatments were not given, but hCG was administered at follicle ≥35 mm. Mares were inseminated with fresh semen, and embryo recovery attempts were performed 8 d postovulation. Synchrony of ovulations within each group appeared to be similar. Six mares in the eFSH group failed to ovulate. The eFSH treatment resulted in higher (P < 0.05) numbers of preovulatory follicles and ovulations; however, embryo recovery rate did not increase (eFSH 1.0 ± 0.4 vs. control 0.95 ± 0.1 embryos/recovery attempt), and embryo per ovulation rate was significantly lower (36% vs. 73%). The eFSH-treated mares had significantly higher frequency of nonovulatory follicles (28% vs. 0) and higher periovulatory serum concentrations of estradiol-17β. Based on our findings, combined P&E and eFSH regimens cannot be recommended for cycling donor mares.     

Identification and partial characterization of Rhizopus nigricans Gβ proteins and their expression in the presence of progesterone

The mammalian steroid hormone progesterone actuates a signalling pathway in the zygomycete Rhizopus nigricans which includes heterotrimeric G proteins. To investigate the possibility that the Gβ subunit of these proteins is involved in the signalling, a cDNA library from R. nigricans exposed to progesterone was prepared and a sequence coding for a Gβ subunit was searched for. Using degenerate primers, two sequences, RnGPB1 and RnGPB2, were identified that exhibited a high degree of identity with those for Gβ from other filamentous fungi, but not from yeast. The presence of more than one Gβ subunit is very rare among the fungi, and it has been to date reported only for Rhizopus oryzae. We have shown that progesterone increases the expression of RnGPB1, but has no influence on the expression of RnGPB2. Therefore, our studies imply the involvement of Gβ subunit 1 in the response of R. nigricans to progesterone. Moreover, the Gβ subunit is subjected to endogenous ADP-ribosylation in the presence of NAD, which could be important in some, as yet unknown, cell process. Article from a special issue on steroids and microorganisms.     

Luteal progesterone and prostaglandin F2α production invitro during fluprostenol-induced luteolysis in the mare

Prostaglandin F₂α (PGF₂α) release $\text{in}$$\text{vitro}$ by luteal tissue from mares was quantified to determine if exogenous prostaglandin analog increased endogenous luteal PGF₂α production during induced luteolysis. On day 8 after ovulation, luteal tissue was collected by flank laparotomy and endometrium was collected by uterine biopsy. Mares were assigned to one of four treatments: (1) no intramuscular injection at 0-hr (n = 5), (2) 250 μg Fluprostenol (ICI 81008 PGF₂α analog) at 4-hr (n = 4), (3) 250 μg Fluprostenol at 12-hr (n = 5), or (4) 250 μg Fluprostenol at 28-hr (n = 5) prior to tissue collection at laparotomy. Blood was collected from a jugular vein at laparotomy. Luteal and endometrial tissues (100-mg minces) were incubated in duplicate in 5 ml of Krebs-Ringer bicarbonate buffer (pH 7.4) in an ice bath in an air atmosphere or at 37°C in an atmosphere of 95% O₂:5% CO₂. The incubation treatments consisted of: no treatment, indomethacin 1.3 × 10^?4M, 1 μg/ml of arachidonic acid, 10 μg/ml of Fluprostenol, and 100 μM dbc-AMP (Fluprostenol was not added to endometrial tissue incubations). The injection of Fluprostenol induced luteolysis in these mares as indicated by decreased plasma progesterone and luteal tissue progesterone production (P<0.01). Luteal PGF₂α production was only detectable in tissue from mares that had been injected with Fluprostenol; production reached a maximum by 12 hr post-injection and had returned to pre-treatment levels by 28 hr (P<0.01). Endometrial tissue produced PGF₂α, but this activity was not significantly affected by injection of mares with Fluprostenol. Increased production of PGF₂α by luteal tissue of mares during PGF₂α analog induced luteolysis was similar to that observed in the pig and ewe.     

Distribution and hormonal regulation of membrane progesterone receptors β and γ in ciliated epithelial cells of mouse and human fallopian tubes

Background  

The controlled beating of cilia of the fallopian tube plays an important role in facilitating the meeting of gametes and subsequently transporting the fertilized egg to its implantation site. Rapid effects of progesterone on ciliary beat frequency have been reported in the fallopian tubes of cows, but the identity of the receptors mediating this non-genomic action of progesterone is not known. We recently identified a member of the non-genomic membrane progesterone receptor family, mPR gamma, as a candidate for mediating these actions of progesterone. Here, we investigated the possible presence of a related receptor, mPR beta, in the fallopian tubes of mice and women as well as the possible hormonal regulation of mPR beta and gamma.     

Effects of oestradiol-17β and progesterone on total and nuclear-protein synthesis in epithelial and stromal tissues of the mouse uterus, and of progesterone on the ability of these tissues to bind oestradiol-17β

1. A method is described for separating uterine epithelium that is 80% pure and connective-tissue stroma that is 60% pure. This was used to study the effects of steroid hormones on total and nuclear-protein synthesis in these tissues. 2. Oestradiol-17beta given alone produces mitoses in the epithelium but not in the stroma. It stimulated incorporation in vitro of [(14)C]lysine into total protein, histones and acidic nuclear proteins to a greater extent in epithelium than stroma. Incorporation into acidic nuclear proteins was most markedly stimulated, reaching four to six times the normal value 4h after treatment, and then declining rapidly. This peak was only seen in epithelial preparations. 3. After pretreatment with progesterone, oestradiol-17beta has the reverse effect, producing mitoses only in stroma. Progesterone alone had no effect on the amounts or rates of incorporation of [(14)C]lysine into stromal nuclear proteins, but changes after oestradiol-17beta treatment were similar to those seen in epithelium with oestradiol-17beta alone. In the epithelium, progesterone alone depressed incorporation into histones and acidic nuclear proteins, but did not abolish the subsequent response to oestradiol-17beta. With this treatment there was a rapid, large and transient increase in incorporation into epithelial total protein not seen with oestradiol-17beta alone. 4. Progesterone had no qualitative effect on the distribution of specific oestrogen-binding proteins, as judged by sucrose-density-gradient centrifugation. However, progesterone treatment increased the uptake in vivo of [6,7-(3)H]oestradiol-17beta by stroma, and it is possible that this is important although the differences were not apparent after labelling in vitro.     

Relationships between the incidence of pre-ovulatory behaviour and the concentrations of oestradiol-17β and progesterone in bovine plasma

The incidence of eleven components of behaviour exhibited by 24 British Friesian heifers, housed in three groups of eight, was recorded for 24 days. All observed behaviour involved the participation of two individuals, these being within groups. The identity of the heifer initiating each behavioural event and that of the one receiving it was recorded. Thus the incidence of 11 “initiating” components and 11 “receiving” components, in effect the incidence of 22 different (but related) components, was recorded throughout an oestrous cycle for all heifers.Components were classified into four groups: standing, mounting, initiating behaviour (other than mounting) and receiving behaviour (other than standing). There was a peak in the incidence of all four groups around the time of oestrus, standing being uniquely, and mounting very highly, associated with the state of oestrus.Plasma oestradiol-17β levels rose steadily during 4 days to a peak, at about the time of onset of the greatly increased incidence of behaviour at oestrus, when progesterone levels were low. Oestradiol-17β levels then declined rapidly to a low level within 12 h of the end of the period of increased incidence of behaviour. No correlation was found between the magnitude of individual, peak, pre-oestrus levels of plasma oestradiol-17β and the incidence of any of the four groups of behavioural components.It is suggested that the limits of the time period when oestrous behaviour is shown are controlled mainly by oestradiol-17β, probably by the timing of its retention by receptors in cells of target brain tissues. The incidence of behavioural events during this period is, however, in part controlled by the presence or absence of a second oestrous heifer.A second smaller peak of plasma oestradiol-17β occurred 5 days after oestrus, when plasma progesterone was about one-third of peak luteal phase levels. No increase in incidence of behaviour was associated with this oestradiol-17β peak.     

Estradiol and progesterone receptor concentrations and 17β-hydroxysteroid-dehydrogenase activity in estrogenprogestin stimulated endometrium of women with gonadal dysgenesis

Four hypergonadotrophic women between 25 and 37 years of age with gonadal dysgenesis were treated sequentially with estrogens and a progestin. The hormonal environment induced by this therapy was similar to that of ovulating women, as demonstrated by serum levels of estradiol, endometrial histology and pituitary gonadotropin secretion before and after LH-RH double stimulation.The concentrations of estradiol and progesterone receptors (ER and PR) and the activity of the 17β-hydroxysteroid-dehydrogenase (17β-HSD) were determined in endometrial curettings obtained from the above patients at 5 different days of their 28-day artificial cycles. The results were correlated to the histology of the endometrium and the serum concentrations of estradiol at the corresponding days of the cycle.The cytoplasmic ER and PR concentrations in the endometrium were 3–6 times higher during the estrogen than progestin phase of the induced endometrial cycle. For the activity of the 17β-HSD, the contrary was the case, being 6–10 fold higher during the progestin phase. A 22-day administration of estrogens only did not lead to a rise in enzyme activity or decrease in receptor content as observed under progestin influence after day 14. Since ER and PR concentrations and 17β-HSD activities were similar to those in the endometrium of normally ovulating women, these results confirm experimentally the present concept concerning the dependence of the cytoplasmic ER and PR content and 17β-HSD activity on female sex hormone action.     

Do small and large luteal cells of the sheep interact in the production of progesterone?

Corpora lutea from cyclic ewes were dissociated by collagenase and trypsin/EGTA treatments, and enriched fractions of small and large luteal cells were prepared on gradients of Ficoll. These fractions were incubated separately or remixed before incubation. Colchicine, cytochalasin B and the calcium channel-blocker verapamil significantly reduced progesterone production by both small and large luteal cell fractions, while isoprenaline stimulated an increase in progesterone production by large luteal cell fractions only. When fractions of small and large luteal cells were remixed, no more and no less progesterone was produced than would have been predicted from equivalent fractions incubated separately. There was therefore no evidence of synergism between small and large luteal cells in the production of progesterone. Prostaglandin F-2 alpha, which can inhibit LH-stimulated progesterone production by ovine luteal tissue in vitro, had no effect on LH-stimulated progesterone production by small luteal cell fractions, but significantly inhibited that by enriched fractions of large luteal cells. Since large luteal cell fractions were contaminated with small luteal cells, which are probably responsible for the progesterone-secretory response of these fractions to LH, it was concluded that the inhibition of LH-stimulated progesterone production by small luteal cells is dependent on the presence of large luteal cells. Oxytocin added to large and small luteal cell fractions did not affect progesterone production by either fraction. It was therefore concluded that the inhibitory action of PGF-2 alpha on LH-stimulated progesterone production may require the interaction of large and small luteal cells, but that oxytocin is not likely to be an intermediary in this interaction.     

Does exogenous progesterone and oestradiol treatment from the mid-luteal phase induce follicular cysts in goats?

The purpose of the present study was to investigate the effects of exogenous ovarian steroid treatment, which is known to induce follicular cyst experimentally in cows, on ovarian activity in goats. Eleven female Shiba goats with the length of the normal oestrous cycle (approximately 21 days) received subcutaneously either 1 ml of ethanol (control group, n=4) or 4 mg of progesterone and 2mg of oestradiol (treatment group, n=7) daily for 7 days beginning on day 14 of the oestrous cycle (day 0=ovulation). Ultrasonographic images of the ovary and blood samples were collected daily to monitor the ovarian activity. Ovulation was observed before 1 day after the end of treatment in the control group. In the treatment group, no detectable structures of follicles or corpus luteum (static ovarian condition) were found for 6.0+/-1.4 days (mean+/-S.D.) after the end of treatment. Then, detectable follicles appeared and ovulation was observed in all animals of the treatment group. There was no significant difference in the maximum diameter of the ovulatory follicle between the control and treatment group (4.7+/-0.4mm versus 5.1+/-0.7 mm). The large non-ovulatory follicles, which grew more than 10mm in diameter were observed after the static ovarian condition in one goat of the treatment group, whereas no turnover of the cystic follicular structures was found. The length of the inter-ovulatory intervals in the treatment group was significantly longer than that in the control group (38.4+/-7.4 days versus 20.3+/-0.5 days, P<0.05). The present results demonstrated that the exogenous treatment of progesterone and oestradiol, which was adapted from the follicular cyst model in cows, did not induce follicular cysts in goats, suggesting that there is/are different mechanism(s) mediating the occurrence of follicular cysts between cows and goats.     

3D models of lamprey progesterone receptor complexed with progesterone, 7α-hydroxy-progesterone and 15α-hydroxy-progesterone

Sea lamprey, a basal vertebrate, contains a progesterone receptor [PR]. An unusual property of lamprey is that gonadotropin-releasing hormone induces synthesis of 15α-hydroxy-progesterone [15α-OH-P] instead of progesterone. There also is indirect evidence for 7α-OH-P in lamprey serum. To determine if there is a structural basis for the binding of 7α-OH-P and 15α-OH-P to lamprey PR, we constructed 3D models of the lamprey PR complexed with progesterone, 7α-OH-P and 15α-OH-P. These 3D models reveal that Met-277 in lamprey PR has a specific interaction with the 15α-hydroxyl on 15α-OH-P and with Met-192, which also contacts the 15α-hydroxyl group. We also find that 7α-OH-P has favorable contacts with side-chains in lamprey PR. BLAST searches reveal that Met-277 on lamprey PR is unique among vertebrate PRs. This unique site on lamprey PR could be a target for compounds to control reproduction in sea lamprey, an environmental pest in Lake Michigan.     

Age-dependent changes in fecal 17β-estradiol and progesterone concentrations in female spider monkeys (Ateles geoffroyi)

The objective of this study was to investigate whether sex steroids decreased with age in female black-handed spider monkeys (Ateles geoffroyi). Fecal concentrations of 17β-estradiol and progesterone (five samples/wk) and the number of ovulatory and anovulatory cycles were compared between adult (n = 3) and aged females (n = 2). All animals (regardless of age) had higher 17β-estradiol concentrations during the fertile than the nonfertile phases. However, during the fertile phase, concentrations of this hormone were significantly higher in adult females. Conversely, progesterone concentrations varied normally throughout the menstrual cycle in both adult and aged animals, with no significant difference between age classes. Similarly, there was no significant effect of age on the number of ovulatory and anovulatory cycles. In conclusion, we inferred that the aged female spider monkeys did not reach menopause, instead they remained in a perimenopausal period characterized by changes in fecal concentrations of ovarian steroids and hypothalamus-hypophysis-ovary axis activity, as well as irregular menstrual flows, for prolonged intervals.     

Prostaglandin f2α induced termination of pregnancy and its reversal by prolactin or progesterone in rats

Intrauterine insertion of a Silastic-PVP tube containing 400 μg PGF_2α terminated midterm pregnancy in 100 percent of the animals. Progesterone (2 mg/day) or prolactin (PRL) reversed the abortifacient effect of PGF_2α. A dose- and duration-related effect of the PRL on PGFinduced termination of pregnancy was evident. The results suggest that PP 2 and PRL are antagonistic to each other and multiple doses of PRL are needed to neutralize the luteolytic action of PGF_2α.     

Isolation,identification and quantitation of serum 5α-pregnane-3,20-dione and its relationship to progesterone in the pregnant mare

5α-pregnane-3,20-dione was isolated from pooled pregnant mare serum using Sephadex LH-20 column chromatography and identified by the use of radioimmunoassay, gas-liquid chromatography and gas-liquid chromatography-mass spectrometry analyses. 5β-pregnane-3,20-dione was not cross-reactive with the radioimmunoassay system and was not detected by gas-liquid chromatography. Peripheral blood levels of progesterone and 5α-pregnane-3,20-dione were determined by radioimmunoassay in four Quarter Horse mares for the first 150 days of gestation. Progesterone and 5α-pregnane-3,20-dione declined from a range of 6 to 15 ng/ml at day 10 to a range of 2 to 8 ng/ml at day 40. After day 40 there was an increase in progesterone and 5α-pregnane-3,20-dione concentration. Toward the end of 150 days of gestation progesterone tended to decline whereas, 5α-pregnane-3,20-dione levels were maintained or increased to levels as high as 35 ng/ml. Neither source nor function of 5α-pregnane-3,20-dione is known.     

Modulation of human β-defensin-2 expression by 17β-estradiol and progesterone in vaginal epithelial cells

We investigated the expression of HBD-1 and -2 in vaginal epithelial cells treated with lipopolysaccharide (LPS) and the effects on HBD-2 expressions by 17β-estradiol and progesterone. Primary vaginal epithelial cells were isolated from a segment of normal anterior vaginal wall obtained during vaginoplasty and were cultured in keratinocyte growth medium and were allowed to undergo their 3rd passage. Expression of HBD-1 and -2 by different stimuli using LPS 0.5 μg/ml, 17β-estradiol 2 nM and progesterone 1 μM was measured by RT-PCR, ELISA and real-time RT-PCR, respectively. HBD-1 was produced constitutively in vaginal epithelial cells and the production of HBD-1 was not influenced by LPS, 17β-estradiol and progesterone, but the production of HBD-2 was increased inducibly by LPS. 17β-Estradiol and progesterone did not change the production of HBD-2 in normal state, but 17β-estradiol increased the production of HBD-2 and progesterone suppressed the production of HBD-2 under the circumstances with infection. The HBD-2 plays an important role at innate host defense on genitourinary tract. The lacks of estrogen during menopause or uses of a progesterone-based oral contraceptive in sexually active women may influence production of HBD-2 in vaginal epithelium and may increase susceptibility to bacterial vaginitis or recurrent UTI.