Intrauterine cortisol, aldosterone, and corticosteroid binding globulin-like activity during early porcine pregnancy and the estrous cycle

Studies were conducted to determine whether the corticosteroids cortisol and aldosterone, and corticosteroid-binding globulin (CBG) were present in the porcine early-embryonic environment. Cortisol was measured in uterine flushings from white crossbred gilts at Days 7, 10, 13, and 16 of the estrous cycle and pregnancy. Total content of cortisol increased (p < 0.01) between Days 13 and 16, and immunoreactive CBG (ir-CBG) increased (p < 0.01) between Days 10 and 13, in both cyclic and pregnant gilts. In a separate study with Chinese Meishan gilts, total cortisol and aldosterone content of uterine flushings increased (p < 0.02) between Days 10 and 15 of the estrous cycle and pregnancy. In another study with white crossbred gilts, CBG-like binding activity in uterine flushings was low at Day 10, then increased over 100-fold at Day 15 (p < 0.01). However, levels of CBG-like binding activity on Day 15 were 100-fold lower than those of ir-CBG measured in the previous study and could bind less than 4% of the uterine luminal cortisol. Differences between ir-CBG and CBG binding might be due to the ability of the CBG antibody to recognize either biologically inactive CBG or structurally similar molecules. CBG-like binding activity, which appeared unrelated to glucocorticoid receptors, was also present in the endometrial cytosol of white crossbred gilts. Concentrations (fmol/mg protein) of endometrial CBG-like activity decreased (p = 0.03) between Days 10 and 15 of the estrous cycle and pregnancy, did not differ with reproductive status, and on Day 15 were comparable to concentrations in uterine flushings but threefold lower (p < 0.01) than those in the serum. Equilibrium dissociation constants for CBG-like binding activities were comparable among the three locations. These studies indicate that corticosteroids are present-primarily in the free form-within the porcine uterine lumen and could influence early porcine conceptus development. Endometrial CBG-like binding activity could mediate actions of cortisol or progesterone on uterine function.     

Effect of the conceptus and lack of effect of uterine space on endometrial protein secretion during mid-gestation in swine

The effect of the conceptus and of reduced uterine space on endometrial protein secretion was examined on Days 40, 60, and 80 of gestation in white crossbred gilts. Twenty-nine gilts were checked daily for estrus, and 15 were given 5 mg estradiol valerate daily from Days 11 to 15 (Day 0 = day of estrus) of the estrous cycle to induce pseudopregnancy. The remaining 14 pigs were mated during estrus. All pigs were laparotomized on Day 4, and one uterine horn was ligated to produce one crowded and one roomy uterine environment. Pigs were killed on Days 40, 60, and 80 of pregnancy or pseudopregnancy. The reproductive tracts were collected, and placental tissues from pregnant pigs and endometrial tissues from all pigs were cultured in the presence of 3H-leucine to evaluate protein secretion. Conditioned medium was dialyzed, measured for incorporation of radioactivity into nondialyzable macromolecules, and then subjected to two-dimensional (2D)-PAGE to determine the effect of uterine space and day of pregnancy or pseudopregnancy on overall protein secretion rate and secretion of specific proteins. Fetal survival, fetal weight, and placental weight were decreased (p < 0.01) in the crowded uterine environment compared to the roomy uterine environment. Incorporation of 3H-leucine into nondialyzable macromolecules by endometrial tissue in culture was not affected by uterine space. Secretion of nondialyzable macromolecules by endometrium from pregnant pigs was not different from that by endometrium from pseudopregnant pigs on Day 40 but was greater (p < 0.01) on Days 60 and 80.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monitoring of isotretinoin therapy by measuring the plasma levels of isotretinoin and 4-oxo-isotretinoin. A useful tool for management of severe acne

Folate-binding proteins (FBP) from Day 60 pseudopregnant uterine flushings and Day 60 allantoic fluid were purified by affinity chromatography on folate-Sepharose followed by G-100 Sephadex chromatography. FBP from uterine flushings had a molecular weight of 20000; the N-terminal sequence was FNWDHXGKMEPAXKRHFXXXTXLYX, which is 72% identical to bovine milk FBP beginning at amino acid 64. Allantoic fluid FBP had a molecular weight of 30000; and the N-terminal sequence ARAKTDMLNVXMDAKHHKPKPSXED, which is 68% identical to bovine milk FBP starting at amino acid 4. Scatchard analysis of purified allantoic fluid FBP using [3H]folic acid as ligand indicated a dissociation constant of 0.54 nM, and the protein was saturated at 20 nM. Antiserum to the purified allantoic fluid FBP was generated in rabbits and used for immunoblotting. Uterine flushings were collected from pregnant and nonpregnant gilts on Days 10, 11, 12, 13, and 15. Immunoblotting indicated that FBP concentrations increased in uterine flushings from both pregnant and nonpregnant gilts between Days 10 and 15. Total uterine flush specific binding of [3H]folic acid increased from 0.015 nmol on Day 10 to 2.14 nmol on Day 15. These results indicate that an FBP similar to other known FBPs is present in uterine flushings and allantoic fluid and that its level increases at about the time of blastocyst elongation and initiation of conceptus hematopoiesis. These results suggest a role for FBP in the delivery of folate to the developing conceptus.     

The impact of participation in a study abroad programme on students'' conceptual understanding of community health nursing in a developing country

Porcine uterine tissues were collected from Days 10 to 14 of gestation (peri-implantation period) or corresponding days of the estrous cycle. Results indicated a marked increase in beta transforming growth factors (TGFbeta1, TGFbeta2, and TGFbeta3) and TGFbeta receptor (type I and type II) immunostaining in uterine luminal epithelium (ULE) between Days 10 and 14 of gestation, but there was no increase in ULE immunostaining on the corresponding days of the estrous cycle. Uterine glands and stroma were intensely immunopositive in pregnant gilts for TGFbeta isoforms and their receptors, but immunostaining was weak to undetectable in cycling gilts. No differences were detected in myometrium, in which immunostaining was moderate in both cycling and pregnant gilts. Additionally, TGFbeta2 and TGFbeta receptor (type I and type II) immunostaining was detected in uterine monocyte/macrophage-like cells. Western blotting detected the presence of all three TGFbeta isoforms in uterine luminal flushings. The CCL64 cell TGFbeta bioassay detected bioactive TGFbetas++ in uterine luminal flushings on Days 12, 13, an 14 of gestation. These results strongly indicate that uterine expression of TGFbetas and their receptors is pregnancy specific and that bioactive TGFbetas are present at the conceptus-maternal interface in the peri-implantation period in pigs. Thus TGFbetas are likely to be involved in autocrine-paracrine interactions between the maternal uterus and the conceptus.     

Reproductive performance in relation to uterine and embryonic traits during early gestation in Meishan, large white and crossbred sows

Previous studies have shown that females of the Chinese Meishan breed and of their F1 cross with European Large White pigs are very prolific, producing about four more piglets per litter than control Large White females. The main cause of this prolificacy is enhanced prenatal survival for a given ovulation rate in Meishan and F1 females and this is controlled by genes of the mother, not those of the conceptus. The objectives of this study were to determine whether genotypic differences in embryo survival were apparent in the period immediately after attachment and to compare embryonic and uterine development at this time. Sows in their third parity (20 Large White, 14 Meishan, 25 Large White x Meishan F1 and 25 Meishan x Large White F1) were killed 20-22 days after mating and their reproductive tracts recovered for further study. There were significant differences between the purebred sows, and crossbred sows were approximately intermediate for the number of corpora lutea (20.7 +/- 0.9, 27.8 +/- 1.1, 22.4 +/- 0.8 and 23.3 +/- 0.8 for the four genotypes, respectively), the number of embryos (15.2 +/- 0.9, 23.4 +/- 1.1, 17.2 +/- 0.8 and 18.8 +/- 0.8, respectively) and the proportionate embryo survival (0.74 +/- 0.04, 0.84 +/- 0.04, 0.78 +/- 0.03 and 0.82 +/- 0.03, respectively). There was a negative association within genotype between embryo survival and the number of corpora lutea. Adjusting for the genotypic difference in the number of corpora lutea increased the genotypic differences in embryo survival.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of the vascular endothelium on norepinephrine-induced contractions in uterine radial arteries from the nonpregnant and pregnant human uterus

OBJECTIVE: Our purpose was to investigate the role of the endothelium in the human uterine arterial response to norepinephrine in the nonpregnant and pregnant states. STUDY DESIGN: Tissue was obtained from six pregnant and six nonpregnant women undergoing cesarean section or hysterectomy. Uterine radial arteries were isolated and subjected to norepinephrine dose-response curves with and without intact endothelium. RESULTS: Responses were obtained over a dose range of 10(-8) to 10(-4) norepinephrine. Initially there was no difference between vessels from pregnant and nonpregnant patients, but removal of the endothelium significantly increased the response in vessels from pregnant women. Addition of nitro-L-arginine methyl ester when the endothelium was intact did not alter the dose-response curves. CONCLUSIONS: In pregnancy human uterine radial arteries are more sensitive to norepinephrine than during the nonpregnant state. This increase is countered by an endothelium-derived relaxing factor. The factor is unlikely to be nitric oxide.     

Pregnancy increases soluble and particulate guanylate cyclases and decreases the clearance receptor of natriuretic peptides in ovine uterine, but not systemic, arteries

Pregnancy increases uterine blood flow by 30- to 50-fold and uterine production of cGMP by 38-fold. Moreover, cGMP causes potent vasodilatation. We hypothesized that pregnancy up-regulates soluble and particulate guanylate cyclases (sGC and pGC) in ovine uterine arteries. Activities of sGC and pGC were compared by measuring cGMP production (37 C; 10 min) by uterine arteries from nonpregnant (n = 5) and pregnant (n = 4, 120 +/- 2 days' gestation; term = 145 +/- 3 days; mean +/- SE) ewes after sodium nitroprusside (100 microM), atrial natriuretic peptide (1 microM), or C-type natriuretic peptide (CNP; 1 microM) treatment. The protein and/or messenger RNA expressions of sGC beta1-subunit, pGC-A, pGC-B, the clearance receptor of natriuretic peptide (CR), and CNP were investigated in uterine and systemic (renal and/or omental) arteries from nonpregnant (n = 29) and pregnant (n = 21; 125 +/- 2 days' gestation) ewes. The potencies of uterine arterial GC activities were sGC > pGC-A > pGC-B. Activities as well as protein expression of sGC, pGC-A, and pGC-B in pregnant uterine arteries were increased 48-128% above those in nonpregnant controls concomitant with a 34% down-regulation of CR protein expression; systemic arterial protein expressions were unaltered. These changes in uterine arterial GC-B and CR were confirmed using RT-PCR. Immunohistochemical staining of CNP in uterine, but not systemic, arterial endothelium from pregnant ewes was much stronger than that from nonpregnant ewes. Thus, two distinct GC pathways are present in ovine uterine artery, and both may be specifically upregulated during pregnancy and so contribute to the tremendous local increase in cGMP production during pregnancy.     

IFN-tau: a novel subtype I IFN1. Structural characteristics, non-ubiquitous expression, structure-function relationships, a pregnancy hormonal embryonic signal and cross-species therapeutic potentialities

IFN-tau (IFN-tau) constitutes a new class of type I IFN which is not virus-inducible, unlike IFN-alpha and IFN-beta, but is constitutively produced by the trophectoderm of the ruminant conceptus during a very short period in early pregnancy. It plays a pivotal role in the mechanisms of maternal recognition of pregnancy in ruminants and it displays high antiviral and antiproliferative activities across species with a prominent lack of cytotoxicity at high concentrations in vitro in cell culture and possibly in vivo. It exhibits high antiretroviral activity against HIV and exhibits immunosuppressive activity in a multiple sclerosis model and reduces embryo and fetal mortality by stimulation of IL-10 production. In this review all the biochemical and para-hormonal properties of this novel IFN-tau are described in detail: structural characteristics of proteins and genes, trophoblast expression, regulation of its expression, structure of its gene promoter, its absence in human species and in non-ruminant animals, the evolution of the IFN-tau genes, its structure-function relationships with its three-dimensional structure, structural localization of biological activities, its lack of cytotoxicity and its receptor. Surprisingly, for an IFN, IFN-tau is also a pregnancy-embryonic signal with paracrine antiluteolytic activity. In order to maintain luteal progesterone secretion, IFN-tau inhibits PGF-2alpha pulsatile secretion and oxytocin uterine receptivity in early pregnancy. It is believed to suppress pulsatile release of endometrial PGF-2alpha by preventing oxytocin and estrogen receptor expression. Additionally, it directly regulates prostaglandin metabolism and possibly the PGE:PGF-2alpha ratio.     

Growth hormone, prolactin and chorionic somatomammotropin in normal and molar pregnancy

Twenty patients with molar pregnancy, ten normal pregnant women and ten healthy non-pregnant women were given 30 g of arginine intravenously. The serum concentration of growth hormone, prolactin and chorionic somatomammotropin (CS) was determined by radioimmunoassay. In addition, serum 17beta-estradiol, estriol and progesterone were also measured. Arginine infusion induced a sharp rise of GH in patients with molar pregnancy and in nonpregnant subjects, but the response in normal pregnancy was blunted. The response of PRL was high in patients with molar pregnancy, blunted in normal pregnancy and very small in nonpregnant subjects. CS did not respond at all to arginine infusion both in normal pregnancy and molar pregnancy. The high response to argine of PRL, normal response of GH and low baseline secretion and no response of CS may be characteristic of molar pregnancy.     

On the essential oil of green algae. II. The oils of the genera Ankistrodesmus and Scendesmus

Uterine arteries from pregnant and nonpregnant patients were studied to define their responses to lidocaine. Although local anesthetics usually are considered vasodilators, these data indicate that the human uterine artery constricts when exposed to 1,000 mug of lidocaine in vitro. Furthermore, those arteries from pregnant patients exhibited significantly greater responses than did those from nonpregnant patients.     

Endothelin receptor type A and B gene expression in human nonpregnant, term pregnant, and preeclamptic uterus

OBJECTIVE: The aim of this study was to quantify the gene expression of ETA and ETB receptors within the different uterine segments of nonpregnant, normal pregnant, and preeclamptic women. STUDY DESIGN: Biopsy samples from the cervix, isthmus, and corpus uteri were obtained from eight nonpregnant, nine term pregnant, and seven preeclamptic women. The concentration of ETA and ETB receptor messenger ribonucleic acid were determined by a solution hybridization technique with complementary ribonucleic acid probes. Results are presented in counts per minute per microgram of total nucleic acid as mean +/- SEM. RESULTS: The expression of messenger ribonucleic acid encoding the ETA receptor was generally higher in the upper than in the lower uterine segment in nonpregnant, normal pregnant, and preeclamptic myometrium, whereas the opposite pattern was seen with regard to ETB. During normal pregnancy the concentrations of ETA receptor messenger ribonucleic acid in the corpus and ETB receptor messenger ribonucleic acid in the isthmus were significantly elevated compared with those in nonpregnant women. This enhanced gene expression was, however, not observed in the preeclamptic group. CONCLUSION: Our finding of segmentally differentiated endothelin receptor gene expression is compatible with a role for endothelin-1 in stimulating uterine contractions through ETA receptors during spontaneous labor and suggests a relaxing effect of the ETB receptor on the myometrium.     

Endothelin-1 and endothelin receptors are present in the sheep uterus and conceptus at implantation

Previous studies have demonstrated that endothelin is present in the ovine endometrium and increases at around the expected time of implantation. To characterize further uterine endothelin at the time of establishment of pregnancy in sheep, endothelin was measured by radioimmunoassay in uterine flushings obtained during the oestrous cycle and in pregnant ewes up to the time of implantation (day 16). During the oestrous cycle, the highest amounts of endothelin were present in uterine flushings on day 14 (1.1 +/- 0.2 ng endothelin/uterus). During early pregnancy, basal levels of endothelin (0.5-0.6 ng endothelin/uterus) were present in uterine flushings for the first 10 days and then increased on day 14 to levels similar to those found at the equivalent stage of the oestrous cycle. On days 15 and 16 of pregnancy, endothelin content in the uterine lumen increased to significantly (P < 0.05) higher concentrations (2.9 +/- 0.4 ng endothelin/uterus) when compared with the non-fertile cycle. The principal isoform present in flushings at the time of implantation was endothelin-1, as determined by reverse-phase HPLC. Endothelin was released principally by purified endometrial epithelial cells in culture, with barely detectable amounts released by endometrial stromal cells or conceptus tissue, which is consistent with the epithelium being the principal source of endothelin in the uterine lumen. Endothelin binding sites were present in endometrium and myometrium, as demonstrated by specific binding of 125I-labelled endothelin-1, which was saturable and displaced by endothelin-1. Both endothelinA and B sub-types of receptors were present as demonstrated by the biphasic displacement of 125I-labelled endothelin-1 binding by the specific endothelinB agonist BQ3020. These were localised principally on luminal and glandular epithelium and in the vasculature of the endometrium and myometrium as shown by autoradiography. Endothelin receptors were also present on the conceptus obtained at the time of implantation. In the day 20 conceptus, endothelin immunostaining was localised principally in the heart, in trophoblast in uninucleate but not in binucleate cells, and in fetal membranes. This immunostaining of the conceptus may represent binding to receptor sites. It is concluded that endothelin-1 is present in the uterine lumen and may play an important role in the paracrine regulation of the conceptus and endometrium at the time of rapid embryo development, implantation and early placentation.     

Pregnancy increases ovine uterine artery endothelial cyclooxygenase-1 expression

During normal pregnancy, and especially in the third trimester, both uterine blood flow and prostacyclin production by ovine uterine arteries are dramatically increased. We sought to determine if this is due, in part, to an increase in cyclooxygenase (COX) expression in the uterine artery endothelium. In this study we compared COX expression in uterine artery endothelium from nonpregnant and third-trimester pregnant (110-142 days' gestation) ewes. COX-2 expression was not detectable by Western blotting in uterine artery endothelium or vascular smooth muscle (VSM). In contrast, COX-1 expression was clearly observed in uterine artery. Immunohistochemical localization of COX-1 was endothelium > VSM, with both cell types showing an increase in COX-1 during the third trimester of pregnancy. COX-1 protein and messenger RNA (mRNA) levels were also detectable in collagenase dispersed endothelial cells, with expression of COX-1 in uterine artery endothelial cells dramatically increased during the third trimester of pregnancy at both the level of protein (346.4 +/- 28% of nonpregnant controls, P < 0.0005) and mRNA (51.04 +/- 7.98-fold of nonpregnant controls, P < 0.001). We conclude that the pregnancy-induced increases in prostacyclin production by uterine arteries is largely due to a dramatic increase in expression of COX-1 mRNA and associated protein predominantly occurring in the uterine artery endothelium and, to a lesser extent, in the VSM.     

Uterine secretion of prostaglandin F2 alpha in the ewe: regulation at the cellular level by ovarian hormones and the conceptus

Changes in the ability of the uterus to secrete prostaglandin F2 alpha (PGF2 alpha) in response to oxytocin may play a critical role in determining when endogenous secretion of PGF2 alpha begins. The cellular mechanisms that regulate uterine secretion of PGF2 alpha in response to oxytocin have not been completely defined. Several intracellular components that may contribute to this regulation have been studied, including phospholipase C (PLC), prostaglandin H endoperoxide synthase (PGS) and receptors for oxytocin. All of these components change during the oestrous cycle and are associated with the development of uterine secretory responsiveness to oxytocin. Progesterone appears to play the principal role in regulating oxytocin receptors, PLC and PGS. The conceptus appears to suppress the increase in receptors for oxytocin and PLC activity that typically occurs around the time of luteal regression.     

Effects of 16,16-Dimethyl-trans-delta 2-PGE1 methyl ester (ONO-802) on uterine, placental and ovarian circulation (author's transl)

Doses of the drugs which produce uterine contraction were given intravenously to various species of animals. Placental and ovarian circulations were measured by the thermocouple method and/or microangiography. Uterine arterial blood flow (UABF) was measured by the electromagnetic flowmeter. Both placental blood flow (PBF) and UABF decreased with the administration of ONO-802, PGE1 or PGF2 alpha to to rabbits and dogs. Oxytocin and noradrenaline also decreased PBF in rabbits. ONO-802 or PGE1 lowered arterial blood pressure (BP) in rats, rabbits and dogs. PGE2 alpha elevated BP in rats and dogs and lowered it in rabbits. Oxytocin produced no changes in PB while noradrenaline elevated BP in rabbits. Ovarian blood flow in pregnant rabbits was reduced by ONO-802, PGE1 or PGF2 alpha. Little influence was seen with oxytocin. Regarding the luteal microvasculature in pregnant rats, ONO-802, PGF2 alpha and noradrenaline exhibited vasoconstricting effects. PGF2 alpha induced abortion and decreased plasma progesterone levels. These results suggest that the inhibitory effects of ONO-802 on the uterine and placental circulation are strongly influenced by the uterine contractile effect and that the inhibitory effect on the ovarian circulation in rats is one of pharmacological effects not concerned with the abortifacient or luteolytic effect.     

Inhibition of oxytocin receptor function by direct binding of progesterone

The steroid hormone progesterone (P4) is essential for establishing and maintaining pregnancy in mammals. One of its functions includes maintenance of uterine quiescence by decreasing uterine sensitivity to the uterotonic peptide hormone oxytocin. Although it is generally held that steroid hormones such as P4 act at a genomic level by binding to nuclear receptors and modulating the expression of specific target genes, we show here that the effect of P4 on uterine sensitivity to oxytocin involves direct, non-genomic action of P4 on the uterine oxytocin receptor (OTR), a member of the G-protein-coupled receptor family. P4 inhibits oxytocin binding to OTR-containing membranes in vitro, binds with high affinity to recombinant rat OTR expressed in CHO cells, and suppresses oxytocin-induced inositol phosphate production and calcium mobilization. These effects are highly steroid- and receptor-specific, because binding and signalling functions of the closely related human OTR are not affected by P4 itself but by the P4 metabolite 5beta-dihydroprogesterone. Our findings provide the first evidence for a direct interaction between a steroid hormone and a G-protein-coupled receptor and define a new level of crosstalk between the peptide- and steroid-hormone signalling pathways.     

Interrelationships between dietary protein level, energy intake, and nitrogen retention in pregnant gilts

Two experiments were conducted to study the effects of dietary protein levels and DE intake on N retention in pregnant gilts. Thirty-two gilts were used in Exp. 1 to investigate the response to eight levels of dietary CP ranging from 50 to 235 g/kg (3.3 to 14.5 lysine/kg). Gilts were given 1,400 g of feed daily throughout pregnancy; diets contained similar balances of amino acids and similar amounts of DE (3.60 to 3.63 Mcal/kg). Thirty gilts in Exp. 2 were allocated during pregnancy to six levels of feeding ranging from 1.1 to 3.1 kg/d. The common diet given to gilts contained 3.49 Mcal of DE/kg, 155 g of CP/kg, and 10.7 g of lysine/kg and was considered adequate in protein. Nitrogen balance trials were conducted during early, mid-, and late pregnancy and collection periods of 5 d duration commenced on d 30, 58, and 86 in Exp. 1 and d 30, 58, and 93 in Exp. 2. The average live weights of pigs on all treatments within each collection period were similar and were 112.5, 123.3, and 136.6 kg and 120.7, 136.3, and 158.3 kg in Exp. 1 and 2, respectively. At each stage of pregnancy increments of dietary protein increased N retention up to an inflection point, after which N retention remained at a constant level. The maximum rates of N retention, 10.0, 12.1, and 16.5 g/d during early, mid-, and late pregnancy, occurred at 142, 133, and 162 g of CP/kg, respectively; the corresponding dietary lysine:DE values were 2.4, 2.3, and 2.7 g of lysine/Mcal of DE.(ABSTRACT TRUNCATED AT 250 WORDS)     

Corticotropin-releasing hormone and proopiomelanocortin-derived peptides are present in human myometrium

CRH and POMC-derived peptides are produced at a number of intrauterine sites in both the nonpregnant and pregnant states. It is hypothesized that CRH and POMC-derived peptides may be produced locally by the uterus to modulate myometrial contractility. This study has examined the distribution of these peptides in human uterine tissue during the ovulatory cycle and pregnancy. The immunoperoxidase staining method was used to localize CRH and POMC-derived peptides: ACTH, beta-endorphin, and alphaMSH. Immunoreactive (IR-) CRH and IR-POMC-derived peptides, beta-endorphin and alphaMSH, were observed in the myometrial smooth muscle, vascular smooth muscle, endometrial glandular epithelium, and luminal epithelium of the nonpregnant uterus (n = 17). Staining for IR-CRH did not change during the cycle from the proliferative (n = 8) to the secretory phases (n = 9). Conversely, staining for IR-beta-endorphin and IR-alphaMSH was only observed during the secretory phase of the cycle (n = 9). In uterine tissue obtained from pregnant women (n = 20) IR-CRH was present in the myometrial smooth muscle, vascular smooth muscle, decidua, and glandular epithelium. IR-POMC-derived peptides were not detectable at any uterine site during pregnancy (n = 20). IR-CRH was measurable in myometrial extracts collected from pregnant women undergoing cesarean section (20.9+/-3.8 ng/g wet wt; n = 7) and from nonpregnant premenopausal women undergoing hysterectomy (7.7+/-2.1 ng/g wet wt; n = 6). IR-CRH concentrations significantly increased with pregnancy. Levels of messenger ribonucleic acid encoding for CRH were examined in nonpregnant (n = 4) and pregnant (n = 10) myometrial smooth muscle and were also significantly increased with pregnancy. This study has demonstrated that levels of CRH and POMC peptide in human uterine tissue change with pregnancy and that CRH is produced locally by myometrial smooth muscle cells. These studies are consistent with the possibility that the CRH peptide has an autocrine/paracrine activity during pregnancy and labor that may be related to the modulation of myometrial contractility.