Spontaneous Luteolysis Research Articles

Endocrine changes associated with spontaneous luteolysis in sows. I. Temporal relationships among prolactin, prostaglandin F 2α, progesterone and LH

Five multiparous sows were cannulated via the cephalic and utero-ovarian vein during the mid-luteal phase. Blood samples were drawn hourly for assessment of prolactin, luteinizing hormone (LH), progesterone and prostaglandin F 2α (PGF 2α). Both peripheral prolactin and PGF 2α utero-ovarian venous concentrations increased following luteolysis. After luteal regression, episodic pulse height of prolactin and PGF 2α increased 2.5 and 2.0-fold, respectively. A tendency for synchrony of the prolactin and PGF 2α pulses was observed when progesterone utero-ovarian venous concentrations declined below 100 ng/ml plasma. Peripheral LH concentrations were essentially similar throughout the experiment with smaller fluctuations after luteolysis. The coincidental occurrence of prolactin and PGF 2α pulses suggests a temporal relationship may exist between these hormones during the post-luteal period.

Effect of continuous infusion of oxytocin on length of the oestrous cycle and luteolysis in cattle

In Exp. I oxytocin (60 micrograms/100 kg/day) was infused into the jugular vein of 3 heifers on Days 14-22, 15-18 and 16-19 of the oestrous cycle respectively. In Exp. II 5 heifers were infused with 12 micrograms oxytocin/100 kg/day from Day 15 of the oestrous cycle until clear signs of oestrus. Blood samples were taken from the contralateral jugular vein at 2-h intervals from the start of the infusion. The oestrous cycle before and after treatment served as the controls for each animal. Blood samples were taken less frequently during the control cycles. In Exp. III 3 heifers were infused with 12 micrograms oxytocin/100 kg/day for 50 h before expected oestrus and slaughtered 30-40 min after the end of infusion for determination of oxytocin receptor amounts in the endometrium. Three other heifers slaughtered at the same days of the cycle served as controls. Peripheral concentrations of oxytocin during infusion ranged between 155 and 641 pg/ml in Exp. I and 18 and 25 pg/ml in Exp. II. In 4 our of 8 heifers of Exps I and II, one high pulse of 15-keto-13,14-dihydro-prostaglandin F-2 alpha (PGFM) appeared soon after the start of oxytocin infusion followed by some irregular pulses. The first PGFM pulse was accompanied by a transient (10-14 h) decrease of blood progesterone concentration. High regular pulses of PGFM in all heifers examined were measured between Days 17 and 19 during spontaneous luteolysis. No change in length of the oestrous cycle or secretion patterns of progesterone, PGFM and LH was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of an antiprogesterone (RU486) on the hypothalamic-hypophyseal-ovarian-endometrial axis during the luteal phase of the menstrual cycle.

The impact of the antiprogesterone RU486 [17 beta-hydroxy-11 beta-(4-dimethylaminophenyl) 17 alpha-(1-propynyl)estra- 4,9-dien-3-one] on the hypothalamic-pituitary-ovarian-endometrial axis was examined in normal cycling women during the mid (MLP)- and late (LLP) luteal phases. During the MLP, 10 women received 3 mg/kg RU486 for 3 days. During the LLP, a single dose of 600 mg RU486 was administered to 4 women, and in another 4 women a single dose of 3 mg/kg was given during corpus luteum rescue by hCG. Longitudinal studies with daily and frequent blood samples (every 10 min for 10 h) were conducted during 3 consecutive cycles (control-treatment-recovery). During the MLP, RU486-induced uterine bleeding occurred in all 10 women 36-72 h after the first dose. No histological evidence of endometrial breakdown was found in endometrial biopsies taken 12-24 h before the onset of bleeding. Significant decreases in LH secretion (P less than 0.001) and LH pulse amplitude (P less than 0.006) and blunted pituitary responses to GnRH (P less than 0.01) were evident by the last treatment day, but LH pulse frequency did not change. Complete luteolysis occurred in 2 of the 10 women. Incomplete luteolysis occurred in 8 women and was associated with an initial decline of serum estradiol (P less than 0.001), but not progesterone levels, followed by rebound increases (P less than 0.001) in LH, estradiol, and progesterone levels 3 days later, which may have reversed the luteolytic processes and prolonged corpus luteum function. Spontaneous luteolysis ensued 3-5 days later with the onset of second episodes of uterine bleeding. For serum FSH, an early rise occurred during the luteal phase in advance of the onset of the second episodes of uterine bleeding. This rise may have resulted in early follicle recruitment and accounted for the shorter duration of the follicular phase during recovery cycles. During the LLP, the single RU486 dose resulted in significant decreases in LH pulse amplitude (P less than 0.03), frequency (P less than 0.05), and secretion (not significant) within 12 h. The recovery cycle was entirely normal. Corpus luteum rescue with incremental doses of hCG did not prevent uterine bleeding after RU486 treatment. These findings indicate that RU486 operates at multiple sites and implies that progesterone is important in the control of luteal function. Further, our data provide a basis for exploring the potential use of RU486 as a once a month birth control agent.

Catecholamine content and adenylate cyclase activity in corpora lutea of different ages of the PMSG-treated immature rat

The Catecholamine content and adenylate cyclase response were studied in a well-characterized corpus luteum model, where ovulation was induced by treatment of prepubertal Sprague-Dawley rats with pregnant mare's serum gonadotropin. The luteal content of noradrenaline, determined with HPLC, was constant during the first 7 days of pseudopregnancy, followed by a 3-fold increase in older corpora lutea. No detectable amounts of dopamine were found, while trace amounts of adrenaline were found in a few cases. The increase in noradrenaline content was not associated with a changed sensitivity of luteal adenylate cyclase to catecholamines. The response to adrenaline was maximal in 3-day-old corpora lutea, whereafter a decrease was seen. The significance of the increased endogenous levels of noradrenaline at the end of pseudopregnancy is at present unknown. However, the fact that the increase in noradrenaline occurs a few days before spontaneous luteolysis is of special interest, since it has been suggested that an adrenergic innervation is a prerequisite for the antigonadotropic effect of prostaglandin F 2α in the human corpus luteum.

Luteal contraception

The impact of oral administration of RU 486 on the ongoing functional activity of the hypothalamic-gonadotropin-corpus luteum-endometrial (H-P-CL-E) axis was assessed during the mid-luteal (MLP) and the late-luteal phase (LLP) with and without hCG-induced pseudopregnancy. Longitudinal studies with daily dosing and frequent blood sampling were conducted during three consecutive cycles (control/treatment/recovery). During MLP, uterine bleeding occurred in all subjects within 36–72 h of the first dose of RU 486, but no histological changes were discernible on endometrial biopsy taken 12–24 h before bleeding. There was a significant decrease in LH secretion, pulse amplitude but not frequency. Response to GnRH on the last day of treatment was impaired. This was followed 3 days later by a rebound LH secretion lasting for 5 days. These events were accompanied by an initial decline of estradiol, but not progesterone, and a second peak of 5 days' duration for both estradiol and progesterone. Hence corpus luteum function was prolonged by 5 days, and second bleeding ensued following the spontaneous luteolysis. Recovery cycles were normal. During LLP, a single dose of RU 486 induced uterine bleeding in all cases. This was associated with a decreased LH pulse amplitude and frequency, and a faster decline of both estradiol and progesterone as compared to control cycles. Rescue of corpus luteum function by the administration of incremental doses of hCG failed to prevent the uterine bleeding after a single dose of RU 486. Recovery cycles were normal. While the antiprogesterone effect of RU 486 at the endometrial level was predictably expressed, its effects at the H-P-CL-E axis were also demonstrated. These findings provide important clues for the design of once-monthly contraceptive methods.

Plasma concentrations of oxytocin, prostaglandin and ovarian steroids during spontaneous luteolysis in the cow

Fifteen, non-milking cyclic Holstein heifers and cows were used to study possible hormonal correlations during spontaneous luteal regression. Peripheral plasma samples were assayed for oxytocin, 13,14-dihydro-15-keto-prostaglandin F 2α (PGFM), estradiol-17β and progesterone. On day 9, when luteolysis does not normally occur, no significant elevation in oxytocin or PGFM values occurred in five cows sampled for 12 hr at 15 min intervals. A correlation did not exist (P>.05) between PGFM and oxytocin values nor between estradiol and oxytocin values at this time. Of 10 cows bled on day 18 or 19 for 12 hr at 15 min intervals or 34 hr at 1 hr intervals, five animals exhibited pulsatile elevations of PGFM and oxytocin. The elevations in plasma concentrations of these two hormones were coincident and significant correlation coefficients (P<.01) were calculated (range 0.62 to 0.85). No significant correlation was present in the remaining 5 cows. These results suggests that ovarian oxytocin is secreted concomitantly with uterine prostaglandin production at the time of spontaneous luteolysis in the cow.

Growth and regression of ovarian follicles during the follicular phase of the oestrous cycle in heifers undergoing spontaneous and PGF-2 alpha-induced luteolysis.

Ultrasonography was used to monitor the growth, ovulation and regression of individual ovarian follicles greater than or equal to 5 mm during the late luteal and follicular phases of the oestrous cycle in heifers treated with injections of PGF-2 alpha to induce luteolysis and in heifers undergoing spontaneous luteolysis. Six heifers were given a single injection of PGF-2 alpha between Day 12 and 15 of the oestrous cycle and their ovaries were examined daily by transrectal ultrasonography until ovulation occurred. Another group of 5 heifers was examined daily by ultrasound from Day 14 or 15 of the cycle through spontaneous luteolysis and ovulation. Blood samples were taken twice daily from this group and analysed for progesterone to determine when luteolysis occurred. All heifers were checked for oestrous behaviour twice daily. Mean diameters of ovulatory follicles on each of the 3 days before oestrus were not different between PGF-2 alpha-treated and untreated heifers. In both groups there was large variation among heifers in the sizes and growth rates of the ovulatory follicles. At 3 days before oestrus the diameters of ovulatory follicles were between 7.5 and 11 mm in PGF-2 alpha-treated heifers and between 6 and 11.5 mm in untreated heifers. Non-ovulatory follicles decreased in size during the 3 days before oestrus and the number of non-ovulatory follicles within the size ranges of ovulatory follicles decreased. The ovulatory follicle was not consistently the largest follicle on the ovaries until the day of oestrus but was always one of the 2 largest follicles during the 3 days before oestrus.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxytocin is luteolytic in the rhesus monkey (Macaca mulatta).

Oxytocin (10 mi.u./microliter/h) or vehicle (0.5% chlorobutanol in saline, 1 microliter/h) was chronically infused directly into the corpus luteum of normally cyclic rhesus monkeys, by means of an Alzet pump-ovarian cannula system. Infusion of oxytocin (N = 6) or vehicle (N = 5) began 6 days after the preovulatory oestradiol surge, and daily peripheral blood samples were taken. Oxytocin caused a significant (P less than 0.05) decrease in progesterone, beginning 1 day after treatment, and oestradiol after 4 days; progesterone and oestradiol remained significantly depressed until menstruation. However, peripheral LH concentrations remained unchanged. The duration of the luteal phase, menstrual cycle and the onset of menses from the initiation of oxytocin infusion were significantly (P less than 0.01) shorter when compared to those of vehicle-treated controls. These results show that oxytocin can induce functional luteolysis in the primate and supports the hypothesis that oxytocin of luteal origin may play a role in spontaneous luteolysis.

Changes in plasma concentrations of LH, progesterone and oestradiol in relation to the occurrence of luteolysis, oestrus and time of ovulation in the Shiba goat (Capra hircus).

Luteolysis in Shiba goats was spontaneous (N = 5) or induced by prostaglandin F-2 alpha (N = 5). Blood sampling and the test for oestrous behaviour were carried out at 2-h intervals, and the time of follicular rupture (ovulation) was determined by culdoscopic observations performed every 2 h around the periovulatory period. In both groups plasma LH concentrations showed a temporary but significant increase during the abrupt fall in plasma progesterone concentrations at luteolysis. This LH rise may be responsible for the preovulatory development of antral follicles and the increase in oestradiol secretion from them. The total number of antral follicles (spontaneous luteolysis 3.6 +/- 0.6, induced luteolysis 4.2 +/- 0.7; mean +/- s.e.m.) and the number of ovulations (1.8 +/- 0.4, 2.4 +/- 0.2) did not differ significantly between the two groups. There was also no significant difference in the timing of oestrus, LH surge and ovulation following the two modes of luteolysis. The interval from luteolysis to the peak of the LH surge averaged 65 h (range 56-72 h). The period of oestrous behaviour coincided with the acrophase of the LH surge and lasted for 22 h (12-28 h). Ovulations occurred 21 (16-24) h after the LH peak and 7 (2-12) h after the end of oestrus.

Luteolysis in the rhesus monkey: Ovarian venous estrogen, progesterone, and prostaglandin F 2α-metabolite

The role of prostaglandin F 2α (PGF 2α) in luteolysis in the non-human primate is poorly understood. We have recently reported that chronic PGF 2α infusion to the corpus luteum via Alzet pump, induced premature, functional luteolysis in the rhesus monkey. In the present study we sought to determine the ovarian events leading to spontaneous luteolysis in the monkey. Rhesus monkeys underwent laparotomy during the early luteal (4–5 days after the preovulatory estradiol surge, PES), mid-luteal (7–9 days PES), and late luteal (10–14 days PES) phases or at the first day of menses (M). Concentrations of progesterone, estradiol, estrone, and 13, 14-dihydro-15-keto-PGF 2α (PGFM) were measured in the ovarian venous effluents ipsilateral and contralateral to the ovary bearing the corpus luteum. Steroid levels in the ovarian vein on the corpus luteum side were significantly higher than the non-corpus luteum side throughout the cycle. PGFM levels were similar on both sides until the late luteal phase, when the effluent of the ovary bearing the corpus luteum contained significantly more PGFM (206±3) vs. 123±9 pg/ml, mean±sem); this disparity increased further at the time of menses (241±38 vs. 111±22 pg/ml). These data are the first to show an asymmetric secretion of PGFM in the ovarian venous effluent in the primate and suggest that PGF 2α of ovarian and possibly of corpus luteum origin may be directly involved in luteal demise.

Effects of clomiphene on luteal function in the nonpregnant cynomolgus macaque.

Although estradiol-17 beta (E2) induces premature regression of the corpus luteum (CL), its role in spontaneous luteolysis which occurs at the end of the nonfertile cycle has not been demonstrated. We compared the effects of an estrogen antagonist on E2-induced and spontaneous luteolysis by administering clomiphene (10 mg/day) to cynomolgus macaques during the luteal phase in the presence and absence of exogenous E2 (supplied by subcutaneous Silastic implants). Other animals received either vehicle or E2 implants. Luteal function was assessed by progesterone concentrations and luteal phase length. Clomiphene maintained normal luteal function in the presence of luteolytic levels of E2 in five of six monkeys. However, clomiphene alone did not prolong luteal function beyond that observed in monkeys receiving vehicle. To assess the direct effect of clomiphene on the CL, we incubated monkey luteal cells with human chorionic gonadotropin and clomiphene, E2, or clomiphene plus E2. Clomiphene (1500 ng/ml) alone and E2 (1000 ng/ml) alone significantly (P less than 0.05) inhibited progestin production. Clomiphene and E2 together depressed progestin production to an even greater extent. The data suggest that the mechanisms involved in E2-induced and spontaneous luteolysis differ.

Growth and differentiation of large antral follicles after spontaneous luteolysis in heifers: changes in concentration of hormones in follicular fluid and specific binding of gonadotropins to follicles.

The objective of the present study was to characterize changes in growth, concentrations of steroids in follicular fluid (FF) and gonadotropin receptors of individual antral follicles after spontaneous luteolysis in heifers and to reexamine our hormonal method of classifying healthy and atretic follicles. Groups of heifers were ovariectomized (OVX) before regression of corpora lutea on d 17, 18 and 19 of an estrous cycle and after regression of corpora lutea at time periods before, during and after preovulatory gonadotropin surges. Each follicle greater than or equal to 6 mm in diameter was examined for concentration of progesterone, androstenedione, testosterone and estradiol-17 beta in FF and capacities of granulosal and thecal cells to specifically bind 125I-bovine follicle stimulating hormone (bFSH) or 125I-human chorionic gonadotropin (hCG). Follicles were separated into two classes, estrogen-active (E-A) or estrogen-inactive (E-I). Concentrations of estradiol in FF were higher than both progesterone and androgens in E-A follicles, whereas either androgens or progesterone was higher than estradiol in E-I follicles. Diameters, volumes of FF and numbers of granulosal cells in E-A follicles increased from d 17 through the end of the preovulatory gonadotropin surges. During this time, concentrations of progesterone, androstenedione and estradiol in FF and specific binding of 125I-hCG to granulosal and thecal cells increased, whereas specific binding of 125I-bFSH to granulosal cells decreased. In E-I follicles, progesterone in FF decreased and androstenedione increased from d 17 through end of gonadotropin surges. The E-I follicles had a higher incidence of granulosal cells with pycnosis than E-A follicles. We concluded that changes in growth, concentration of steroids in FF and gonadotropin receptors in E-A follicles after spontaneous luteolysis were similar to changes we previously reported for E-A follicles after prostaglandin-induced luteolysis, and that ratio of concentration of estradiol in FF to both progesterone and androgens could be used to separate potential ovulatory (E-A) from atretic (E-I) follicles in heifers.

Effect of Inhibition of Estrogen Synthesis During the Luteal Phase on Function of the Corpus Luteum in Rhesus Monkeys 1

It has been hypothesized that estrogen synthesized by the corpus luteum initiates luteal regression during the nonfertile menstrual cycle in primates. To study the role of endogenous estrogens in functional regression of the monkey corpus luteum, we administered the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD) to rhesus monkeys during the luteal phase of the menstrual cycle. Twice-daily oral administration of ATD suppressed systemic and intraluteal estrogen levels by 80-90%. The midluteal phase rise in estradiol concentrations that occurs in rhesus monkeys was completely abolished by ATD treatment. Despite suppression of estrogen synthesis during the luteal phase, mean menstrual cycle length and length of the luteal phase were not different than in control monkeys treated with vehicle only. Progesterone levels were lower in the ATD-treated group on the second and third day of treatment, but did not differ from control levels during the remainder of the cycle. These data suggest that elevated estrogen synthesis during the luteal phase of the menstrual cycle is not a prerequisite for spontaneous luteolysis in rhesus monkeys.

Relationship of estradiol to luteal function in the cycling baboon.

Since exogenous 17 beta-estradiol (E2) is luteolytic in some primates, it is reasonable to conclude that endogenous E2 is the naturally occurring luteolytic substance. However, a link between endogenous E2 and spontaneous luteolysis has not been demonstrated. In an attempt to understand the function of E2 in spontaneous luteolysis, we employed the antiestrogen clomiphene. We administered E2, clomiphene, or E2 plus clomiphene to baboons during the luteal phase and measured systemic levels of estrone, E2, progesterone (P), and LH, E2 alone depressed the concentrations of P and bioassayable LH prematurely. The length of the luteal phase was significantly shortened (12.8 +/- 0.9 vs. 15.8 +/- 0.4 days for sham controls; P less than 0.01). Clomiphene blocked the luteolytic effect of exogenous E2, resulting in P levels which were not significantly different (P greater than 0.01) from control and a luteal phase of normal length (15.0 +/- 1.0 days). Treatment with E2 alone caused serum LH concentrations to decrease. The administration of clomiphene alone maintained circulating LH at early to midluteal phase levels but did not alter luteal phase P concentrations or prolong the length of the luteal phase (15.6 +/- 0.4 days). The results suggest that E2-induced luteolysis is a result of the withdrawal of luteotropic support from the (corpus) luteum, while spontaneous luteolysis is a result of some other mechanism which may not involve endogenous E2.

Luteolysis in the hamster: Abrogation by gonadotropin and prolactin pretreatment

The luteolysis which terminated pseudopregnancy (PSP) in superovulated hamsters was studied. Spontaneous luteolysis occurred before 1100 on Day 7 of PSP and was characterized by a rapid decline in circulating progesterone levels. Luteolysis induced by prostaglandin F 2α (PGF 2α) on Day 5 of PSP displayed a similar rapid reduction in progesterone over 24 hours. In both cases levels of the progesterone metabolite 20α hydroxypregn-4-ene-3-one (20α-OHP) were less than 2 percent of progesterone levels and declined in a manner similar to progesterone. This suggests that conversion of progesterone or its precursors to 20α-OHP was not a functional aspect of luteolysis in the hamster. Pretreatment with either prolactin (PRL), luteinizing hormone (LH) or follicle stimulating hormone (FSH) failed to prevent PGF 2α-induced luteolysis on Day 5 in the superovulated PSP hamster. Combinations of PRL and LH, LH and FSH or PRL and FSH were also unsuccessful in abrogating luteolysis. However, pretreatment with a combination of PRL, FSH and LH prevented luteolysis in 11 14 animals. These results suggest that luteotropic agents can reverse the luteolytic effects of PGF 2α in the hamster.

Estrogen production by luteal cells isolated from rhesus monkeys during the menstrual cycle: correlation with spontaneous luteolysis.

To assess the hypothesis that luteolysis in primates may occur as a consequence of estrogen secretion by the corpus luteum, the production of estradiol (E2), estrone (E1), and progesterone (P) was examined in suspensions of luteal cells isolated from corpora lutea of rhesus monkeys at various stages of the menstrual cycle. Cells were obtained on days 16–19 (5-7 days after the preovulatory LH peak), days 21-22 (8-10 days after the LH surge), and days 23-25 (11-14 days after the LH surge) of the menstrual cycle. Under basal conditions (no exogenous hormones), day 16–19 cells secreted picogram quantities (per 5 × 104 cells/ml nutrient medium) of E2 and E1 compared to nanogram amounts of P for up to 6 h in vitro. Estrogen production by day 16–19 cells was significantly (P < 0.05) enhanced by as little as 0.1 ng/ml hCG, with a maximal response at 100 ng/ml. Under basal conditions, day 16–19 cells produced significantly greater amounts of E2 than E1, whereas day 21-22 cells synthesized similar quantitites of th...

Control of the preovulatory endocrine events in the ewe: interrelationship of estradiol, progesterone, and luteinizing hormone.

Two experiments were conducted to examine the possibility that, in the ewe, regression of the corpus luteum initiates the following series of preovulatory events: 1) a sustained increase in tonic LH secretion resulting from progesterone withdrawal; 2) a sustained increase in estradiol secretion stimulated by the rising titer of LH; and 3) the estradiol-induced preovulatory LH surge. In the first experiment, the corpus luteum was removed surgically during the midluteal phase of the estrous cycle. This procedure induced a premature withdrawal of progesterone accompanied by premature sustained increases in circulating LH and estradiol and a premature preovulatory LH surge. These changes closely resembled those which follow spontaneous luteolysis. The premature sustained increases in circulating LH and estradiol and the LH surge were prevented when luteal phase levels of serum progesterone were maintained by insertion of progesterone implants at the time of corpus luteum removal, and they were reinstated when...

Menstrual cycle characteristics in chronically hemiovariectomized cynomolgus monkeys (Macaca fascicularis).

Circulating levels of LH, FSH, estradiol, and progesterone were measured by RIA in daily serum samples throughout the menstrual cycle in five regularly cycling, chronically hemiovariectomized, adult cynomolgus monkeys. The hormonal patterns, the lengths of the follicular and luteal phases, and the overall cycle length were nearly indistinguishable from those observed in intact cycling monkeys. The findings accord with the notions 1) that in intact monkeys, the contralateral ovary contributes little, if at all, to the regulation of the function or lifespan of the corpus luteum, and 2) that the corpus luteum after spontaneous luteolysis has no local residual effect inimical to new follicle growth.

THE SERUM LEVELS OF PROGESTERONE AND 20α-DIHYDROPROGESTERONE, AND THE OVARIAN LH, FSH AND PRL BINDING DURING LUTEOLYSIS OF THE SUPERLUTEINIZED RAT OVARY

ABSTRACT The process of luteolysis has been studied in immature rats in which superluteinization had been induced with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotrophin (HCG). Following prostaglandin F2α and the prostaglandin analogues, and at the end of the pseudopregnancy, the plasma levels of progesterone and 20α-dihydroprogesterone were measured and used as parameters of luteal function in relation to the capacity of the ovarian tissue to bind LH, FSH and prolactin (PRL) in vitro. On day 19 after HCG a marked decrease in the progesterone level from the day 8 level was observed concomitant with a marked increase in 20α-dihydroprogesterone. The capacity of the ovarian tissue to bind LH in vitro was markedly reduced on day 19 compared to day 8. Identical changes were observed 21 h after 1 mg prostaglandin F2α or prostaglandin analogues. Progesterone decreased from about 600 ng/ml to about 50 ng/ml, whereas the increase in 20α-dihydroprogesterone was from about 200 ng/ml to 500–1000 ng/ml and the reduction in LH binding sites was from 1.7 × 10−12 to 0.5 × 10−12 mol/mg protein. Nanogram amounts of the analogues were as effective as 1 mg of prostaglandin F2α. The number of FSH or PRL binding sites was not affected by spontaneous luteolysis or the treatment given. By the use of graded doses of the prostaglandin analogues a negative correlation (r=−0.81) was found between plasma progesterone and 20α-dihydroprogesterone levels, and a positive correlation (r = 0.84) between LH binding sites and plasma progesterone levels. The luteolysis induced by prostaglandin F2α or prostaglandin analogues was indistinguishable from the spontaneous luteolysis using these parameters.