Uterine Luteolytic Factor Research Articles

Gross Anatomy of the Female Genital Organs of the Pampas Deer (Ozotoceros bezoarticus, Linnaeus 1758)

To describe the macroscopic anatomy of the genital organs of the female pampas deer (Ozotoceros bezoarticus), organs from animals dead in a captive breeding station were dissected. A total of twenty females, 17 adults and 10 pre-puberal approximately 1 year old were studied by gross dissection. The ovaries of adult females without corpora lutea weighed 0.22±0.02 g on the right and 0.20±0.01 g on the left and accounted for 0.03±0.01% of body weight. All corpora lutea (n=6) were found in the right ovary, but in cases where there was no corpus luteum present, the right ovary tended to be heavier than the left (P=0.1). The absence of ovarian bursa, intercornual ligament and suburethral diverticle is peculiar to this deer species. Only 6 convex caruncles were found in the uterine horns, which differ from the more of 100 present in domestic ruminants. Four regular folds that were observed in the cervix of the uterus should not be an obstacle to the passage of a transcervical catheter, allowing intrauterine artificial insemination. The close relationship between the ovarian artery and vein stood up could be associated with the passage of the uterine luteolytic factor from the vein to the ovarian artery, avoiding its systemic way, as happens in domestic ruminants. While the plan of organization was similar, there are some differences with the descriptions of other ruminants. Our results may be very useful as it provides with information that may be considered for the development of female reproductive biotechnologies.

Endocrine and Local Control of the Primate Corpus Luteum: 1973 to Today.Richard L. Stouffer, Ph.D.

Over 25 years have passed since the annual meeting of the Society for the Study of Reproduction included a session on the comparative aspects and advances in our knowledge of the corpus luteum (CL) in rodent, domestic animal and primate species. Using Dr. E. Knobil's 1973 perspective on the nonhuman and human CL as a starting point, key advances particularly over the past decade will be summarized. In addition, the influence of G. Niswender's research, as related to the elucidation of luteal cell types and the differences between luteinizing hormone (LH) and chorionic gonadotropin (CG)-receptor binding and signaling, will be examined. Finally, recurrent questions and opportunities for further research will be highlighted. Collectively, studies employing pulsatile gonadotropin releasing hormone (GnRH) or GnRH antagonist treatment reinforce the concept that pituitary LH is the primary luteotropic hormone in female monkeys and women, but can we rule out a role for other hormones, including prolactin-like factors? And do local effects of GnRH/GnRH antagonist in the CL complicate our interpretation of the results of LH ablation/replacement protocols? With the advent of monkey and human gene arrays, the transcriptome offers insight into LH-regulated genes (both up- and down-regulated) in the CL, but which are directly regulated by LH versus indirectly via LH-modulated local factors, including steroid hormones and growth factors? Our knowledge of the processes controlling CL development, particularly angiogenesis, has increased, but events leading to CL regression near the end of the nonfertile menstrual cycle remain a mystery. Since the life span of the CL during the menstrual cycle is not regulated by a uterine luteolytic factor, Knobil hypothesized that intraluteal "self-desruct" agents are responsible for luteal regression in primates. Are Knobil's candidates, estradiol and prostaglandin F 2alpha, or other agents, the likely factor(s)? What are the roles of theca-derived and granulosa-derived luteal cells, and luteal cell - nonluteal (microvascular; immune) cell interactions in controlling the functional lifespan of the primate CL? Also, what are the qualities of placental, LH-like CG that rescue the CL and extend its function into early gestation? Opportunities remain for innovative research at the systems, cellular and molecular levels to increase our understanding of primate CL structure-function that is relevant to fertility control and women's health. Supported by NIH NICHD R01HD20869, SCCPIR U54HD18185, CDRC U54HD55744; NCRR P51 RR00163; Schering AG.

Characteristics and regulation of the ovarian cycle in vervet monkeys (Chlorocebus aethiops)

This study was designed to evaluate the timecourse of ovarian and pituitary endocrine events throughout the menstrual cycle in the vervet monkey, and whether circulating luteinizing hormone (LH) or the uterus regulates the functional lifespan of the vervet corpus luteum. Daily saphenous blood samples were collected from adult females (1) during spontaneous menstrual cycles (n = 7), and (2) during cycles in which a gonadotropin-releasing hormone antagonist (acyline) was administered for 3 days at midluteal phase (n = 3), and (3) for 30 days following recovery from hysterectomy (n = 4). Estradiol (E) and progesterone (P) levels were assayed using electrochemoluminescent assays. Gonadotropin levels were measured by radioimmunoassay using reagents developed for the assay of follicle-stimulating hormone and LH in macaques. Spontaneous cycles exhibited a midcycle E rise (476+/-49 pg/ml), engendering an LH surge, 12+/-1 days after onset of menses, followed by a luteal phase with peak P levels of 4.7+/-0.9 ng/ml. Histologic evaluation of the ovaries at late follicular phase or early luteal phase revealed the presence of a single, large Graafian follicle or developing corpus luteum, respectively. Acyline treatment caused a significant (P<0.05) decline in P levels (2.9+/-0.5 vs 0.5+/-0.3 ng/ml, 0 vs 48 h post-treatment) and premature menstruation compared with untreated controls (P<0.05). Hysterectomy had no apparent effect on the monthly pattern or levels of circulating E or P. Thus, the characteristics and regulation of the ovarian cycle in vervets appear similar to those in women and macaques, with cyclicity dependent on pituitary gonadotropin hormones and independent of a uterine luteolytic factor.

Biochemical aspects of conceptus--endometrial interactions.

Mammalian conceptuses must provide a chemical signal to the maternal system to insure maintenance of corpus luteum (CL) function and of progesterone production and continuation of uterine endometrial secretory activity. These events insure that the developing conceptus is provided with appropriate nutrients, regulatory enzymes and endocrine state to allow successful establishment and maintenance of pregnancy. Pig blastocysts begin to produce estrogens by Day 11 of pregnancy, which prevents secretion of the uterine luteolytic factor (PGF2 alpha) in an endocrine direction, but allows secretion in an exocrine direction, i.e., into the uterine lumen. Therefore, CL are "protected." Blastocyst estrogens also trigger secretion of a group of proteins, including uteroferrin, an iron transport protein, and a family of protease inhibitors whose biosynthesis within the uterine glandular epithelium is under the control of progesterone. Estrogen also appears to promote accumulation of glucose and fructose within the uterine lumen. A complex in vivo "culture medium" is thereby established to promote conceptus development. Pig blastocysts do not undergo invasive implantation within the uterine lumen although they produce the protease, plasminogen activator. Invasion may be prevented by endometrial secretion of progesterone-induced protease inhibitors which are produced in large amounts. In addition to estrogens of conceptus origin, calcium and prostaglandins PGF2 alpha and E2 may affect the uterine vasculature, water and electrolyte transport, capillary permeability, conceptus steroid production, and related events during pregnancy. The blastocysts of the large domestic animals also secrete proteins which include a large glycoprotein (Mr approximately 600,000) and a small acidic protein (Mr approximately 17,000). The latter has been purified from sheep and named ovine trophoblast protein I. These proteins may play unique roles in early pregnancy with respect to establishment and maintenance of pregnancy in the ewe, sow, mare, and cow.

Luteotropic and antiluteolytic activities of the rabbit conceptus.

We have previously confirmed that maternal recognition of pregnancy in the rabbit occurs between Days 10 and 18 following mating. However, the mechanisms by which the conceptuses affect continued maternal corpus luteum progesterone secretion have not been completely defined. To determine whether the conceptuses develop a gonadotropin-like activity as a function of gestation time, preimplantation embryos collected on Day 6 post coitum (p.c.), early postimplantation conceptuses obtained on Day 10 p.c., and medium from preincubations of fetal placentas obtained on Days 18 and 26 p.c. were tested for their ability to increase testosterone production by dispersed rat testicular interstitial cells. A very low gonadotropin-like activity was evident in post-implantation conceptuses; however, as gonadotropin-like activity in maternal peripheral serum was greater than that observed in uterine venous serum, the significance of a direct gonadotropic signal from the conceptus remains unclear. Furthermore, in an additional bioassay for gonadotropin-like activity, rabbit fetal placentas obtained on Days 17-20 p.c. failed to stimulate ovarian growth and ovulation in immature rats. These data suggest that a direct luteotropic stimulus from the conceptus may not be a significant factor in continued corpus luteum function during pregnancy. Other investigators have reported that the rabbit conceptus plays a role in blocking a uterine induced luteolysis at or near the time of maternal pregnancy recognition. Following hysterectomy of pregnant and pseudopregnant rabbits on Days 6 or 10 p.c., the decline in serum progesterone levels was gradual, but the progesterone levels were significantly different from those of intact pregnant does as early as Days 16-18 p.c. In contrast, after hysterectomy on either Day 18 or 26 of pregnancy, serum progesterone concentrations declined abruptly. These data indicate that removal of a uterine luteolytic factor may only partially sustain corpus luteum function for a brief period of time following pregnancy recognition. An additional antiluteolytic role of the conceptus, in blocking a possible extrauterine prostaglandin mediated luteolysis was examined by treating pregnant rabbits hysterectomized on Day 18 with indomethacm, a potent inhibitor of prostaglandin synthesis. This treatment, initiated immediately postsurgery, failed to prevent the rapid decline in serum progesterone levels following hysterectomy, suggesting that in the rabbit prostaglandins may not be involved as extrauterine luteolytic factors.

Prolongation of the oestrous cycle in cows and ewes after passive immunization with PGF antibodies.

Three cows and 2 sheep were passively immunized against prostaglandin (PG) F on Day 16 and Days 13-15 of the oestrous cycle respectively. The PGF antiplasma was raised in ovariectomized ewes against a PGF-2 alpha-bovine serum albumin complex and showed 100%, 12.5%, 0.3%, less than 0.05% and less than 0.01% cross-reactivity with PGF-2 alpha, PGE-2, PGA-2, PGB-2 and arachidonic acid, respectively. Control animals were given an equivalent amount of ovariectomized ewe plasma. In all passively immunized animals there was evidence of a persistent corpus luteum as indicated by plasma progesterone concentration and the failure of the animals to return to oestrus until at least 29 days after treatment. These data are consistent with previous proposals that PGF-2 alpha is the uterine luteolytic factor in sheep and cattle.

Hysterectomy, decidualization, LH concentrations and corpus luteum function in the rat.

Abstract In 1923 Loeb described that the uterus plays an important role in the control of corpus luteum function in the guinea pig: removal of the uterus resulted in a prolongation of the luteal phase. Similar findings have been reported for several other mammalian species (Anderson, 1972). In the rat, hysterectomy does not alter the duration of the estrous cycle (Perry and Rowlands, 1961), but the duration of pseudopregnancy (the equivalent of the luteal phase in the reproductive cycle of other mammalian species) is extended after hysterectomy. The fact that hysterectomy leads to a prolonged luteal phase in certain mammalian species, pointed to the existence of a uterine luteolytic factor (Schomberg, 1969). Some evidence for the existence of a uterine luteolytic substance is available for the rat. It was shown that after removal of the endometrium the duration of pseudopregnancy was extended to almost that observed in hysterectomized rats (Waynforth, 1965). Hechter, Fraenkel, Lev and Soskin (1940) could reduce in the rat the duration of pseudopregnancy with uterine transplants. Furthermore, the duration of pseudopregnancy was shortened after injections of endometrial suspensions (Bradbury, Brown and Gray, 1950) or aqueous endometrial extracts (Dobrowolski, Snochowski and Stupnicki (1974). These observations suggest that the endometrium is the source of the luteolytic factor, and recently evidence was provided that a prostaglandin could be the uterine luteolytic factor (Pharriss, Tillson and Brickson, 1972; Labhsetwar, 1974). Studies in sheep (McCracken, Carlson, Glew, Goding, Baird, Green and Samuelsson, 1972) and in the guinea pig (Blatchley, Donovan, Horton and Poyser, 1972) have provided some evidence for this concept. Also in the rat a prostaglandin may be the uterine luteolytic factor: treatment with prostaglandin F 2α terminates pseudopregnancy in the rat by reducing ovarian and peripheral progesterone concentrations (Pharriss and Wyngarden, 1969; Behrman, Yoshinaga and Greep, 1971). The fact, however, that only a slight increase in F prostaglandins around day 7 of pseudopregnancy and no increase in E prostaglandins was observed (Saksena, Watson, Lau and Shaikh, 1974) throws some doubt upon the idea that a prostaglandin is the luteolytic factor in the rat. On the other hand, the finding that in a bioassay the dose-response curve of endometrial extract from pseudopregnant rats runs parallel with that of prostaglandin F 2α ; (Dobrowolski et al., 1974) could be considered as evidence that a prostaglandin is the uterine luteolytic factor in the rat. In the present paper the effects of hysterectomy and decidualization on certain aspects of pseudopregnancy in the rat are discussed.

Lysosomal enzyme release from luteinized rat ovaries by prostaglandin f2alpha.

Department of Physiology, New York Medical College, Valhalla, New York 10595, U.S.A. (Received 24th January 1975) Extensive evidence has been amassed which demonstrates that prostaglandin (PG) F2α plays an important role in the regulation of CL function. Recently, several experimental findings have buttressed the hypothesis that PGF2α is the uterine luteolytic factor. It has been reported that PGF2α induces degeneration of the CL of the pseudopregnant rat (Pharriss & Wyngarden, 1969), and other mammals (Duncan & Pharriss, 1970; Kirton et al., 1970; McCracken et al., 1970), that it decreases ovarian progesterone secretion in pregnant and pseudopregnant rats (Behrman et al., 1971b), and that it is identifiable in uterine venous blood of guinea-pigs and sheep toward the end of the oestrous cycle, a time which coincides with luteal regression (Bland et al., 1971; Blatchley et al., 1972). Although these aforementioned data clearly demonstrate the luteolytic properties of PGF

Hormonal and related factors affecting the release of prostaglandin F2α from the uterus

While evidence is accumulating that prostaglandin F2α (PGF2α) is the uterine luteolytic factor in several sub-primate species, factors controlling the release of PGF2α from the uterus are not fully documented. The present study utilizes two models consisting of either the in situ or the autotransplanted uterus of the sheep. Four factors affecting the release of PGF2α from the uterus are described, (a) Ovarian steroid hormones: Spontaneous peaks of estradiol-17β (E2-17β) occur throughout the estrous cycle but it is not until the time of corpus luteum regression that peaks of PGF2α release from the uterus become associated with peaks of E2-17β secretion. When physiological amounts of E2-17β are infused into the arterial supply of the autotransplanted uterus, PGF2α, is released only late in the luteal phase suggesting that a priming effect of progesterone may also be necessary for PGF2α synthesis, (b) Oxytocin: When physiological amounts of oxytocin are infused into the arterial supply of the in situ uterus, uterine tonus and amplitude of contractions increase immediately and are associated with a simultaneous increase in PGF2α release, an effect which varied with the steroid status of the animal. Indo-methacin inhibits the oxytocin-induced release of PGF2α but not uterine contractions even although infusions of PGF2α alone mimic this effect of oxytocin. It is possible that PGF2α released during oxytocin action may have other important physiological functions such as altering uterine blood flow or changing cervical tone. (c) Mechanical stimulation: When the in situ uterus is mechanically stimulated by massaging it for 10 min, a rapid and sustained release of PGF2α occurs only very early and very late in the cycle suggesting a dependence of this stimulus on the steroid hormone status of the animal. Peripheral blood levels of oxytocin were found to be elevated during massage at certain stages of the cycle, suggesting that at least some of the massage-induced release of PGF2α may be mediated through oxytocin action on the uterus, (d) Bacterial endotoxin: Endotoxin has long been known to cause abortion in women as well as in lower species. Recent studies in pregnant mice have implicated uterine PGF2α as the mediator of the abortifacient action of endotoxin. Minute quantities of endotoxin injected into the arterial supply of the uterus produce a marked and immediate increase in PGF2α release, an effect which is abolished by Indomethacin. These studies at the organ level confirm and extend the evidence that the abortifacient action of endotoxin is mediated via the release of PGF2α from the uterus.In conclusion the response of the uterus to a variety of physiological and pathological stimuli appears to center invariably on the release of PGF2α (and possibly other PGs) and evidence exists that this event is wholly or partially dependent on the endogenous steroid status of the animal.

Evidence for Preferential Transfer of Prostaglandin F2α to the Ovarian Artery Following Intrauterine Administration in Cattle1

The effect of sectioning the broad ligament ipsilateral to the corpus luteum on estrous cycle length was evaluated. This surgical procedure ioIated the region of proposed transfer of the uterine luteolytic factor from uterine venous input. The estrous cycles of four of five animals were prolonged to at least 30 days, as judged by plasma progesterone concen- trations and the presence of marked corpora lutea at laparotomy on Day 30. In a second experiment, one of the branches of the ovarian artery was cannulated in the hilus of the ovary in five dairy cows, and 6 mg of prostaglandin Fr,, (PGF�.) was injected into thc lumen of the uterine horn ipsilateral to the cannula on Days 12 or 13 of the cycle. Frequent samples were collected simultaneously from the ovarian artery, carotid artery, and jugular vein. The concentration of prostaglandins of the F series (PCF) was observed to increase rapidly at all three sampling sites following administration of PCF,,,. While the concentra- tion was highest in the carotid and jugular within 5 mm of treatment, the concentration of PGF continued to increase in the ovarian artery to reach a peak 40 mm after treatment and remained at levels significantly greater (p <0.05) than jugular or carotid levels for 80 mm. These data are consistent with the hypothesis of preferential transfer of a uterine luteolytic factor from the uterus to the ovarian artery. Intrauterine administration of 6 mg of PCFwas luteolytic, as judged by a fall in plasma progesterone concentrations and a mean corpus luteum weight of 1.83 ± 0.22 g upon termination of the experiment 72 h after treatment. Peripheral plasma estrone and estradiol-17p levels were observed to increase to a peak 9 h after treatment, after which a slight increase in the mean plasma LH concentration occurred. Ovulation had occurred in four of five animals by 72 h after treatment, although LH peaks of the usual preovulatory magnitude were not observed to precede ovulation in all animals.

The fine structure of the human corpus luteum of term pregnancy

The fine structure of human corpora lutea from term pregnancies is described following preservation in formaldehyde-glutaradehyde fixatives containing trinitrophenol. The morphology of human corpora lutea of term pregnancy is compared with recently published observations of lutein tissue taken during early gestation. Granulosa lutein cells at term resemble granulosa lutein cells taken during early pregnancy with respect to nuclear morphology, the nature and amount of both granular and agranular endoplasmic reticulum, the presence of fine filaments, and cell surface modifications. These observations are correlated with recent data on progesterone secretion by corpora lutea of term pregnancy and support the concept that such corpora are functional. At the same time, differences in the nature or number of mitochondria, Golgi complex, lipid droplets, and microtubules distinguish granulosa lutein cells obtained at different stages of pregnancy. These differences are correlated with published data on serum titers of gonadotrophins which vary during the course of gestation. Possible reasons for the persistence of functional corpora lutea throughout human pregnancy are discussed with respect to relaxin secretion, absence of a uterine luteolytic factor, and serum titers of placental hormones.

Prostaglandin F concentration in the peripheral blood of the ewe during the estrous cycle

Serial levels of PGF were quantitated by radioimmunoassay in the serum of 8 ewes during an induced estrous cycle. Daily samples were obtained via chronic catheterization of the inferior vena cava. Mean PGF levels increased throughout the cycle. In addition, a highly significant peak in the mean PGF level occurred on Day 13 following estrus (Day 12 following the serum LH peak) at a time when luteal progesterone levels remained stable. These observations tend to cast doubt on the physiologic role of PGF as the uterine luteolytic factor.

Prostaglandin F 2α in the uterus of ewes during early pregnancy

PGF 2α has been postulated to be the uterine luteolytic factor. If this is true, then one might expect the levels of PGF 2α to be lower during early pregnancy. However, in the present study levels of PGF 2α were found to be significantly higher in both content (ng) and concentration (ng/gm) in the endometrium of day-13 pregnant ewes (2375, 152 respectively) compared to day-13 nonpregnant animals (1478, 89 respectively). These results imply that the luteotropic effects of the embryo must occur by some mechanism other than inhibition of production or release of the uterine luteolytic factor.

Identification of prostaglandin F 2 in uterine fluid from the non-pregnant sheep with an autotransplanted ovary.

SUMMARY In four sheep with an autotransplanted ovary, cyclic oestrous behaviour was abolished due to the persistence of a corpus luteum in the transplant. Fluid recovered from the uterus was viscous, odourless and sterile, and was present in amounts of 10 to 1900 ml. Uterine fluid contained prostaglandin F2α, the total amount recovered ranging from 150 ng to 7·6 mg (15–4000 ng/ml). The identity of prostaglandin F2α was confirmed by gas chromatography-mass spectrometry. No prostaglandins of the E series were found. Biopsy specimens of the uterine wall showed that the uterine and glandular epithelium comprised tall, columnar cells typical of the luteal phase of the normal cycle. The uterine glands were considerably distended and stromal oedema was appreciable. These findings are discussed in the context of the hypothesis that the uterine luteolytic factor (luteolysin) is prostaglandin F2α.

Regulation of Mammalian Reproduction

130 scientists met in a conference sponsored by the National Institutes of Health to review current research on the regulation of mammalian reproduction. Major topics were 1) how the pituitary function could be regulated 2) how sperm production might be regulated; 3) the process and possible points of intervention in sperm maturation and fertilization; 4) the biology of the ovum; 5) the mechanism of action by which gametes are transported in the Fallopian tubes; and 6) the effect of corpus luteum function. Among findings which appear promising are (1) data which suggests the administration of estrogens might induce ovulation at a time when the endometrium is not prepared for implantation; 2) sperm maturation in the epididymis seems to require a certain hormonal ambience which if changed could have a reversible anti-fertility effect; 3) the fallopian tubes may also require a certain hormonal environment for normal reproductive function and may be an end ocrine target for disrupting the reproductive function; 4) data from some species indicates there is a uterine luteolytic factor which could be developed for use in human fertility control.(AUTHORS MODIFIED)

Regression of the ovine corpus luteum after infusion of prostaglandin F 2 into the ovarian artery and uterine vein.

Prostaglandin F2α (PGF2α) is luteolytic in a number of species and the recent finding of endogenous secretion of PGF2α into the utero—ovarian vein of oestrogen-treated guinea-pigs (Blatchley, Donovan, Poyser, Horton, Thompson & Los, 1971) supports the hypothesis that PGF2α is the uterine luteolytic factor. Because the luteolytic effect of the uterus on the corpus luteum is local, it is necessary that a luteolysin secreted by one uterine horn can cause regression of the corpus luteum on the same side. The present experiments were designed to investigate the effect of PGF2α infused into the ovarian artery or uterine vein of the cyclic ewe. Polyvinyl catheters (o.d. 0·8 mm) were inserted into a branch of one ovarian artery and a branch of the uterine vein on the same side in Merino ewes. The other ovary was removed. On day 6, 7, 8 or 9 of the succeeding

Luteotrophic and luteolytic actions of LH in hypophysectomized, pseudopregnancy rabbits.

The ability of LH to sustain the structure and function of corpora lutea (CL) for one week after hypophysectomy was studied in 95 pseudopregnant rabbits. When administered in large sc doses, 125 or 250 μg twice daily (b.i.d.), LH consistently failed to maintain CL regardless of whether the treatment was initiated between 2 to 3 or at 12 hr after hypophysectomy. FSH likewise failed to maintain the CL, although doses of either 200 or 300 μg b.i.d. prevented follicular regression. When smaller doses of LH were combined with FSH, luteal structure and function were maintained to a variable extent and the degree of maintenance was directly related to the weight of the ovary at autopsy. Since luteal maintenance in the rabbit depends on estrogen, these data suggest that small doses of LH, which sustain estrogen secretion from follicular tissue, will be luteotrophic. Larger doses of LH, which suppress estrogen secretion either by luteinization of follicles or by depletion of cholesterol esters, will be luteolytic. Hysterectomy alone did not prevent luteal regression following hypophysectomy, but a higher incidence of good luteal maintenance was obtained with the LH-FSH treatment in hypophysectomized- hysterectomized rabbits than in hypophysectomized rabbits with intact uteri. Although this finding might reflect the removal of a uterine luteolytic factor, it could also be due to the “sparing” of estrogen after removal of its major target organ. (Endocrinology89: 513, 1971)

UTERINE AUTOTRANSPLANTATION TO THE ABDOMINAL WALL IN THE GUINEA-PIG

SUMMARY A method for autotransplantation of the uterus of the guinea-pig to the abdominal wall is described. Complete uterine autotransplantation by this method caused extended oestrous cycles (mean 24·67 days). Similar transplantation but without disconnexion of the cervical end of the uterus gave rise to cycles of similar length (mean 24·75 days) but transplantation without disconnexion of the tubal ends allowed the occurrence of normal cycles (mean 16·20 days). The site of metabolism of the uterine luteolytic factor is discussed.

Functional activity of the corpus luteum following hysterectomy.

ABSTRACT The role of the uterus in the maintenance and regression of the corpus luteum was investigated in 7 patients who underwent hysterectomy for leiomyomata. Except in one patient, hysterectomy was performed in the postovulatory phase of the cycle. The patients were evaluated by preoperative and postoperative urinary pregnanediol determination, visual inspection of the ovaries and histologic examination of the endometrium. The data indicate that hysterectomy did not prolong the life span of the corpus luteum in the operative cycle, and cyclic ovarian function occurred after the operation. It appears that, in contrast to the situation in lower species, a uterine luteolytic factor is not involved in regulating the life span of the human corpus luteum. A self-regulatory mechanism in the corpus luteum itself is probably involved in the regression of luteal function in the human.

Luteolytic effect of prostaglandin in the guinea-pig.

THE mechanisms involved in the periodic regression of the corpus luteum in mammals showing regular oestrous cycles have been extensively studied, and although there is much evidence for the existence of a uterine luteolytic factor in several species, the isolation of such a factor has proved very difficult1,2. The local nature of the effect of the uterus on the corpus luteum in the guinea-pig seems to indicate that the pituitary is not directly involved3, but efforts to extract an endometrial luteolytic substance have been unsuccessful in this species. The uterus contains several pharmacologically active agents, among them various members of the prostaglandin group of lipids4, and in view of preliminary reports that prostaglandin F2α(PGF2α) is luteolytic in some species5, we decided to test its action in the guinea-pig. Fifty mg of PGF2α was made available for this purpose by Dr B. B. Pharriss and the Upjohn Company.