Arg-7 mutant X wild-type crosses in Chlamydomonas reinhardi: study of the enzyme produced in diploid strains

The concentration of prostaglandin (PG) F-2alpha in ovarian arterial blood was compared to that in aortic and carotid blood at different stages of the ovine oestrous cycle, and its concentration measured in the ovarian artery following the infusion of radioactive PGF-2alpha to the uterine vein. In all cases the concentration of PGF-2alpha increased during passage through the ovarian artery, and the increase was proportional to the log of the concentration in the uterine vein. No such change was observed in the concentration of progesterone in the ovarian artery or of PGF in the uterine artery. It was concluded that PGF-2alpha can be and is normally transferred from the uterine vein to the ovarian artery. These results are compatible with the hypothesis that PGF-2alpha of uterine origin is the normal luteolytic agent in the sheep.     

Effects of genistein and lavendustin on reproductive processes in domestic animals in vitro

The aim of our experiments was to study the influence of genistein [tyrosine kinase (TK) inhibitor with estrogenic activity] and lavendustin A (TK inhibitor without estrogenic activity) on female reproductive processes in domestic animals in vitro. It was found that genistein (0.001-1 microg/ml) increased IGF-I release by cultured bovine and porcine granulosa cells, but decreased its secretion by rabbit granulosa cells (0.01-10 microg/ml). Genistein stimulated progesterone secretion by bovine and rabbit granulosa cells (at 0.01-10 microg/ml), estradiol output by rabbit granulosa cells (at 1 microg/ml) and porcine ovarian follicles (at 10 microg/ml), as well as cAMP production by bovine (at 0.001-1 microg/ml) and rabbit (at 1 microg/ml) granulosa cells. No effects of genistein (at 10 microg/ml) on PGF-2 alpha and progesterone release by porcine ovarian follicles were observed. Genistein significantly (P < 0.05) stimulated the reinitiation and completion of nuclear maturation of porcine oocytes (at 5 microg/ml), as well as the preimplantation development of rabbit zygotes (at 1 microg/ml). Lavendustin A (0.001-1 microg/ml) increased IGF-I release by bovine (but not by porcine) granulosa cells, cAMP release by bovine granulosa cells, and PGF-2 alpha output by porcine ovarian follicles (at 10 microg/ml). Lavendustin (at 1 microg/ml) had no significant effect on IGF-I release by porcine granulosa cells, on estradiol and cAMP output by rabbit granulosa cells, or on progesterone secretion by porcine follicles (at 10 microg/ml). Inhibitory actions of lavendustin (at 10 microg/ml) on estradiol secretion by porcine follicles were also found. Furthermore, lavendustin, like genistein, promoted the reinitiation and completion of meiosis in porcine oocytes. The present study demonstrates a predominantly stimulatory effect of TK inhibition on endocrine and generative processes in domestic animals. The majority of these effects are similar for both compounds, indirectly suggesting that their action is due to tyrosine kinase inhibition and protein kinase A-stimulation, rather than estrogenic activity.     

The reliability and application of clinical judgment in evaluating the use of hospital beds

Six ewes were immunized against a prostaglandin F-2alpha-protein conjugate. Between 24 and 82 days after immunization the regular cyclic occurrence of oestrus was abolished in all six ewes. Further investigations of the immunized animals revealed that the blockade of oestrus was due to a persistence of the CL and the constantly elevated (greater than 2 ng/ml) blood levels of progesterone. Surgical enucleation of the persistent CL was promptly followed by a fall in progesterone concentrations (less than 0-5 ng/ml), normal oestrus and a subsequent return to a state of constantly elevated blood progesterone levels. These results show that neutralization of the biological activity of PGF by active immunization against PGF-2alpha results in a failure of luteal regression and provide evidence that endogenous PGF is involved in normal luteal regression in this species.     

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.     

Regulation of prolactin secretion by adrenal steroids in oestrogen-treated ovariectomized rats: participation of endogenous opioid peptides

The purpose of the present study was to determine whether glucocorticoid inhibition of prolactin (PRL) release in oestrogen-treated ovariectomized (OVX) rats is mediated by endogenous opioid peptides (EOPs). All the animals were OVX and given oestradiol benzoate (OB, 20 microg/rat, s.c.) 2 weeks later (day 0). On day 3 they received vehicle, mifepristone (MIF, 10 mg/kg, s.c.) or hydrocortisone (HYD, 2 mg/rat, s.c.), in combination with the opioid antagonist naloxone (NAL, 2 mg/kg, i.p.) or vehicle. Serum PRL concentration was then measured by RIA at 13.00 and 18.00 hr, to include assessment of diurnal variation of PRL secretion. At 13.00 hr either MIF or NAL alone increased PRL secretion with no additional effect when NAL was combined with MIF. HYD had no significant inhibitory effect, but NAL with HYD increased PRL secretion. At 18.00 hr serum PRL concentration was higher than at 13.00 hr, and not affected significantly by MIF or NAL alone, although PRL secretion was increased by treatment with both. HYD inhibited PRL secretion and this inhibition was prevented by NAL. In a second experiment to distinguish antiglucocorticoid and antiprogesterone effects of MIF, we administered progesterone (2 mg/rat, s.c.) or a specific progesterone antiserum. In contrast with MIF, the progesterone antibody had no effect on PRL secretion at 13.00 hr, nor on the stimulation by NAL, while progesterone (unlike HYD) increased PRL secretion and NAL attenuated this response; this was opposite to the effect of NAL with HYD. Similarly, at 18.00 hr the interaction of MIF and NAL was not explained by antagonism of progesterone. Together, these results indicate inhibition of PRL by glucocorticoids but not progesterone, mediated in part by EOPs. At 18.00 hr endogenous glucocorticoids do not regulate oestrogen-stimulated PRL release, although HYD is inhibitory through EOPs.     

Effect of progesterone on prostaglandin F2 alpha secretion and outcome of pregnancy during cloprostenol-induced abortion in mares

OBJECTIVES: To determine the role of progesterone in the regulation of endogenous prostaglandin F2 alpha (PGF2 alpha) secretion during cloprostenol-induced abortion and to investigate use of progestins to prevent prostaglandin-associated abortion. ANIMALS: 16 pregnant mares. PROCEDURE: To induce abortion, cloprostenol (250 micrograms/d) was administered daily until fetal expulsion or for up to 5 days. In experiment 1, 8 mares, 98 to 153 days' pregnant, received progesterone (300 mg/d) at 24-hour intervals for 5 days, starting 18 hours after the first cloprostenol administration. In experiment 2, 8 mares, 93 to 115 days' pregnant, received altrenogest (44 mg/d) at 24-hour intervals, starting 12 hours after the first cloprostenol administration. Historic control mares, 82 to 102 days' pregnant, received cloprostenol (250 micrograms/d) daily until fetal expulsion. RESULTS: In control mares, fetal expulsion occurred after 2 to 3 cloprostenol administrations and was associated with significant increases in PGF2 alpha secretion. Abortion did not occur in 5 of 8 progesterone-treated mares and 8 of 8 altrenogest-treated mares, and endogenous PGF2 alpha secretion was inhibited, compared with values in aborting mares. CONCLUSION: Circulating progestogen concentrations may have a role in the outcome of pregnancy during prostaglandin-induced abortion. Altered prostaglandin secretion may be a reflection of a direct effect of progesterone or may be caused by the abortion process. CLINICAL RELEVANCE: Progestogens might be useful for prevention of abortion in mares in which pregnancy is at risk owing to diseases that are associated with excess prostaglandin secretion.     

Kinetic analysis of successive reactions catalyzed by bovine cytochrome p450(17alpha,lyase)

Bovine P450(17alpha,lyase) containing an additional four histidine residues at the COOH terminus was expressed in Escherichia coli and purified by one-step column chromatography using Ni-chelate resin. The membrane enzyme was incorporated into liposome membranes having similar lipid composition to that of the endoplasmic reticulum. In the presence of excess substrate, the P450-proteoliposomes metabolize pregnenolone (Delta5-steroid) to 17alpha-hydroxypregnenolone and further to dehydroepiandrosterone. The enzyme catalyzed 17alpha-hydroxylation of progesterone (Delta4-steroid) but did not form androstenedione from progesterone, although the proteoliposomes could catalyze the conversion of 17alpha-hydroxyprogesterone to androstenedione. The kinetic analysis of rapid quenching experiments showed that about 20% of the pregnenolone consumed was converted successively to dehydroepiandrosterone via a fraction of 17alpha-hydroxypregnenolone that did not dissociate from the enzyme. The rapid quenching experiments for progesterone metabolism by the proteoliposomes revealed that the dissociation rate of 17alpha-hydroxyprogesterone was 10 times faster than that of 17alpha-hydroxypregnenolone. The release of the intermediate metabolite of Delta4-steroid is sufficiently faster than the lyase reaction to prevent further reaction by the P450. It is concluded that the dissociation rates of the first hydroxylation metabolites regulate the successive reactions of P450(17alpha,lyase).     

Influence of serum, estrogen, and gonadotropins upon growth and progesterone secretion by cultures of granulosa cells from small porcine follicles

Granulosa cells from small (less than 2mm) antral porcine follicles were grown in culture to study the effects of various hormones on growth, morphology and progesterone secretion. Culture medium 199D + 4% serum was found to be most suitable since it maintained a fairly constant cell population. Estradiol (1mug/ml) and human FSH stimulated cell growth. LH and FSH stimulated progesterone secretion and induced morphological changes associated with luteinization. Estradiol (0.1 mug/ml) inhibited progesterone secretion by granulosa cells.     

Total peptic activity in gastric juice and peptic cell mass (chief fundic cells and mucopeptic fundic-antral cells): cellular-secretory correlations in normal subjects

BACKGROUND: This study aimed at determining the turnover rate of parietal cells after inhibition of acid secretion. METHODS: Rats were given omeprazole (80 mumol/kg) by gavage once daily or ranitidine (1200 mumol/kg) by osmotic minipump for 5 days. Control rats received saline only. All rats were also given 3H-thymidine by osmotic minipumps. The animals were killed, 5, 14, 28, or 56 days after the start of the 3H-thymidine infusion. After formaldehyde fixation by perfusion through the aorta, light microscopic autoradiography was carried out on plastic sections of the oxyntic mucosa to determine the labeling index of the parietal cells. RESULTS: The average turnover rate in the control rats was calculated to be 0.61% per day, corresponding to a mean turnover time of 164 days. In the rats given inhibitors of acid secretion, the turnover rates did not differ significantly from those of the control group. CONCLUSION: Inhibition of gastric acid secretion did not significantly change the turnover rate of the parietal cells.     

Effects of ascorbic acid on in vitro steroidogenesis in guinea pigs

Guinea pig ovarian whole tissue homogenates were incubated with [14C]-labelled cholesterol, pregnenolone, and progesterone. Testicular homogenates were incubated with [14C]-progesterone. All incubations were carried out in the presence of 0, 0.5, 1.0, or 2.0 mM ascorbic acid. The conversion of cholesterol to pregnenolone was significantly decreased in testosterone and progesterone production. The addition of 0.5 mM ascorbic acid increased the conversion of pregnenolone to delta 4 steroids and decreased its conversion to delta 5 steroids, relative to the other ascorbic acid treatments. The conversion of progesterone to 17 A-hydroxyprogesterone was significantly decreased in the presence of 1.5 mM ascorbic acid over the O mM treatment. The data supports a general inhibitory effect of high ascorbic acid on the steroid hydroxylations, and a possible regulatory role of ascorbic acid on the conversion of pregnenolone to delta 4 and delta 5 steroids.     

Temporal relationship between progestin and luteinizing hormone concentrations in pseudopregnant rats treated with prostaglandin-F2 alpha

The temporal changes in progesterone (delta 4P), 20 alpha-dihydroprogesterone (20 alpha-DHP) and luteinizing hormone (LH) concentrations in pseudopregnant (PSP) rats after treatment with a single subcutaneous Silastic-PVP tube containing 600 micrograms PGF2 alpha were correlated. Progesterone levels fell and LH levels rose significantly 2h after initiation of treatment, while 20 alpha-DHP levels were found to increase significantly 12h after treatment. Since the changes in delta 4P and LH concentrations occurred concurrently, it seems that the increase in LH levels could have been due to a direct effect of PGF2 alpha on the ovary causing a reduction in delta 4P and thus a negative feedback effect on LH release. Alternatively, PGF2 alpha might exert a direct effect on LH secretion at the hypothalamic-pituitary level.     

Heterotypical sexual behavior in male rats: individual difference in lordosis respones

Castrated Wistar male rats were primed with varying amounts of estradiol benzoate (EB) for successive 2 days and progesterone (P) on the third day 6-8 hr prior to the behavioral test. The tests were performed 4 times at 2-3 weeks intervals. As a priming procedure for the first behavioral test, 50 mug EB and 0.5 mg P were given. The quantity of P was kept constant therafter. For the second test, the dose of EB was increased to 100 mug, but decreased again to 50 mug and further to 10 mug for the third and fourth tests, respectively. The inciedence of animals showing lordosis was quite low, and was not significantly changed by increasing or decreasing the dosage of EB during the series of the behavioral tests. Forty-three out of 51 animals never showed lordosis at all 4 behavioral tests. In contrast, 5 out of 8 rats which responded to mountings by the males continued to display lordosis behavior throughout the series of the successive 4 tests. This consistence of individual responeses during the series of the behavioral tests may indicate the possible existence of individual difference in lordosis responde in male rats.     

Failure of protein synthesis inhibition to block progesterone desensitization of lordosis in female rats

Progesterone's desensitization effect on lordosis has been shown to correlate with a decreased concentration of hypothalamic progestin receptors after progesterone injection. In a recent study, one group of investigators found that the protein synthesis inhibitor anisomycin appeared to block progesterone's desensitization effect. Despite decreased levels of cytoplasmic progestin receptors, progesterone + anisomycin-treated rats exhibited a high level of lordosis four hr after a second progesterone injection. Because this finding conflicts with a progestin receptor model of progesterone's desensitization effect, we investigated it further. In the first experiments, ovariectomized rats were injected with estradiol benzoate followed 24 hr later by either progesterone or vehicle. Anisomycin injected 3 hr after progesterone, at a dose that causes inhibition of hypothalamic protein synthesis for at least 4 hr, was without effect on progesterone desensitization a day later. In other experiments silastic implants containing estradiol were inserted into ovariectomized rats. Forty-five hr later, rats received progesterone or vehicle, followed by injections of anisomycin or saline. Rats receiving anisomycin + progesterone were still highly receptive at 30 hr while saline + progesterone controls were not. Furthermore, the results were similar 4 hr after a second injection of progesterone at 30 hr. In a related experiment, we confirmed that anisomycin delayed dramatically termination of the period of sexual receptivity. In this laboratory anisomycin does not seem to block progesterone's desensitization effect. However, with certain procedures anisomycin delays the termination of sexual receptivity. Thus it is important in investigations of the mechanism of progesterone's desensitization effect that animals be tested prior to the second progesterone injection to determine if they are actually responding to the progesterone.     

Inhibitory effect of a caerulein-like peptide on human gastric secretion

A synthetic heptapeptide corresponding to the C-terminal heptapeptide of caerulein but characterized by a nor-leucyl residue replacing the methyonyl residue of caerulein, when given by i.v. infusion (2 mug/kg/h), inhibited by 70-80% pentagastrin (4 mug/kg/h)-stimulated gastric secretion...     

A comparative study of adrenal progesterone secretion during the estrous cycles of hamsters and rats

Adrenal secretory rates and peripheral plasma levels of progesterone (PROG) were determined during the estrous cycles of hamsters and 4-day cyclic rats. In both species, the PROG concentrations in peripheral plasma were never more than 6% of those observed in adrenal venous plasma. In hamsters, adrenal PROG secretory rates varied from 3.8 +/- 0.8 ng/min at 0800 hr on proestrus (P) to 8.5 +/- 1 ng/min at 2000 hr on estrus (E). The rates noted on P were among the lowest observed and were similar to those noted at 0800 hr the following morning. In rats, adrenal PROG secretory rates varied from 57 +/- 9 ng/min at 0800 hr on E to 130 +/- 18 ng/min at 2000 hr on P. A significant decline occurred between 2000 hr on P and 0800 hr the following morning. Rats secreted 3 to 8 times more PROG than did hamsters when the secretory rates are expressed as ng/min/100 mg adrenal. In hamsters, the data suggest a relative lack of influence of female reproductive hormones on adrenal PROG secretion and in turn the latter may not be involved in reproductive hormonal changes leading to ovulation. In rats, the increased adrenal PROG secretion noted on P may be due to the influence of reproductive hormones on adrenocortical function. This elevated rate may in turn influence the hypothalamo-hypophyseal-ovarian axis.     

Reversal of indomethacin-induced inhibition of tubuloglomerular feedback by prostaglandin infusion

Experiments were performed in rats to study the effect of infusion of PGI2, PGE2, and PGF2 alpha on tubuloglomerular feedback responses (i.e. the change of SNGFR in response to a change of loop of Henle flow rate) in the presence and absence of simultaneous inhibition of endogenous PG synthesis with indomethacin. Infusion of PGI2 or PGE2 at rates that did not alter arterial blood pressure did not significantly modify the magnitude of feedback responses (PGI2 8.5 micrograms/hr, PGE2 85 micrograms/hr). Some inhibition of feedback responses was seen when PGI2 and PGE2 were administered at higher rates that were associated with a reduction of blood pressure (PGI2 20 micrograms/hr, PGE2 200 micrograms/hr). PGI2 (8.5 micrograms/hr) and PGE2 (85 micrograms/hr) largely prevented feedback inhibition induced by indomethacin. When given subsequent to indomethacin PGI2 and PGE2 restored feedback responsiveness almost to normal. In contrast, PGF2 alpha did not influence feedback inhibition caused by indomethacin. Infusion of PGI2 induced partial restoration of feedback responses in DOCA-salt treated animals in which the feedback system is virtually completely inactive. Our results indicate that availability of PGI2 or PGE2 is necessary for the normal operation of the tubuloglomerular feedback mechanism for control of nephron filtration rate.     

Changes in the secretion of ovarian steroid and pituitary luteinizing hormone in the peri-ovulatory period in the ewe: the effect of progesterone

The secretion rates of oestradiol, androstenedione and progesterone and the peripheral plasma concentration of LH were measured in 12 ewes with ovarian autotransplants before and after luteal regression induced by a single intramuscular injection of a synthetic prostaglandin (PG) analogue, 16-aryloxyprostaglandin F 2alpha (I.C.I. 80996). Luteal regression was followed by a fourfold rise in the basal concentration of LH and increased secretion of oestradiol. In five out of six ewes there was a discharge of LH with the peak occurring 36--78 h after the injection of the PG analogue. The secretion of oestradiol declined from 3-68 +/- 1-08 to 0-33 +/- 0-6 (S.E.M.) ng/min in the 24 h following the LH peak (P less than 0-001). In the remaining six ewes in which progesterone was implanted subcutaneously 24 h after the injection of PG analogue, follicular development was suppressed as indicated by the low secretion of oestradiol and androstenedione. The basal concentration of LH fell to values similar to those observed during the luteal phase after the implant of progesterone. The secretion of androstenedione followed a similar pattern to that of oestradiol in those ewes which showed presumptive evidence of ovulation. These results suggest that progesterone reinforces the negative feedback effects of oestrogen in the ewe.     

Angiotensin II effect on plasma steroids in selective hypoaldosteronism

The effect of angiotensin II infusion on plasma pregnenolone, progesterone, corticosterone and aldosterone was investigated in 4 cases of established hypoaldosteronism, in 4 elderly controls in the same age range and in 6 young normals. In young and old normals, angiotensin II induced the expected dose response increase in aldosterone while corticosterone usually decreased progressively during the infusion. Progesterone levels were not significantly different in young and old subjects and no change was observed during angiotensin II infusion. Baseline pregnenolone levels were significantly lower in elderly controls and angiotensin II elicited a slight decrease in pregnenolone in the two control groups. In selective hypoaldosteronism, baseline plasma aldosterone concentrations were very low and the aldosterone response to angiotensin II was blunted. Plasma corticosterone and progesterone levels were in a comparable range to normals throughout the study. Contrary to control subjects, a dose dependent increase in pregnenolone was observed during angiotensin II infusion in the patient group. These results suggest that the anomalies of steroid biosynthesis found in selective hypoaldosteronism could be contributing factors to the hypoaldosteronism in some patients.     

Circulating neutrophils and liver injury in rat models of experimental alcoholic liver disease

The present study examined the effects of progesterone (P4) treatments on estrous cyclicity and the loss of ovarian follicles during aging. Young rats received repeated treatments with P4 or empty implants between 3.5 and 8 mo of age. At 8 mo, ovaries were obtained from some animals to determine the numbers of resting follicles, and estrous cycle patterns and hormone levels were determined from other groups of treated females. In contrast to the cyclic increases in P4, estradiol (E2), LH, and FSH in control animals, P4-implanted rats exhibited elevated serum P4 but low E2, LH, and FSH levels. After implant treatments, the follicular reserve was significantly (p < 0.05) larger in P4-treated females (2012 +/- 297 resting follicles per ovary, n = 5 rats per group) than in regularly cyclic control rats (713 +/- 226 follicles per ovary, n = 7). The effects of P4 implants on the follicular reserve were associated with a subsequently higher incidence of regular estrous cycles after P4 treatment. These results demonstrate that P4 prevents cyclic increases in E2 secretion and is associated with a conservation of the ovarian follicular reserve and the maintenance of regular estrous cycle patterns, indicating a protective effect of P4 on the age-related loss of ovarian follicles.     

The metabolic clearance rates and interconversion of cortisol and cortisone in pregnant and nonpregnant baboons

Pregnancy alters the pattern of maternal cortisol (F) metabolism and increases the maternal serum cortisol-binding capacity (CBC) of baboons. To determine whether these changes are associated with alterations in F clearance,the metabolic clearance rate (MCR) and interconversion (p) of F and cortisone (E) were measured by continuous infusion of (3H)F and (14C)E in 9 regularly menstruating and 7 pregnant baboons (Papio papio). In nonpregnant animals, the values (X +/- SE) for MCR-E (488 +/- 48 1/day) were greater (P less than 0.001) than those for MCR-F (214 +/- 22 1/day). The p value for the conversion of E leads to F (62.8 +/- 4.7%) was greater (P less than 0.001) than that for the reaction F leads to E (41.6 +/- 3.7%), indicating that F formation is favored. Consistent with MCR-E greater than MCR-F, the per cent of F bound to proteins other than albumin (75 +/- 2) was greater (P less than 0.001) than the per cent of E bound (52 +/-3). The production rate (MCR x peripheral concentration; mug/min) of F (55.1 +/- 7.9) was greater (P less than 0.001) than that of E (28.5 +/-3.9) with essentially all of the F being secreted directly (secretion rate 51.2 +/- 7.9 mug/min). Essentially all of the E produced was derived from circulating F, vitually none being secreted directly (secretion rate 4.6 +/- 3.9 mug/min). Pregnancy did not alter the MCR-F (190 +/- 23 1/day), MCR-E 525+/- 51 1/day), per cent of F (79 +/- 3), or per cent of E (49 +/-3) bound,or F (57.2 +/- 9.2 mug/min) or E (35.5 +/- 4.9 mug/min) production rates. CBC (mug F/100 ml) was significantly (P less than 0.01) elevated (25.3 +/- 2.3, nonpregnant vs 35.1 +/- u.6, pregnant). In addition, p E leads to F was increased (75.5 +/- 1.8%) as was p F leads to E (54.3 +/- 3.7%; P less than 0.01). We have concluded that the MCR-F during pregnancy is more dependent on alterations in maternal metabolism than on the increased serum CBC characteristic of gestation. We suggest that the latter factor may be important in regulating the physiologic levels of the other steroids which bind to it.