Follicular development during the luteal phase of the human menstrual cycle

The aims of the present studies were to determine the number, size range, health, and steroidogenic activities of antral follicles in normal human ovaries during the luteal phase of the menstrual cycle. Steroidogenic activity was assessed from the levels of androstenedione, testosterone, and estradiol in follicular fluid and the levels of extant and FSH-stimulable aromatase activity and FSH-stimulable progestin synthesis in the granulosa cells. Data for luteal phase ovaries were compared to those obtained for ovaries from the late follicular phase. On average, 94% (range, 70-100%) of the luteal phase follicles (greater than or equal to 1 mm diameter) were atretic as assessed by oocyte viability and granulosa cell number. The largest healthy follicles during the mid- to late luteal phase were 4-4.5 mm in diameter; these contained high levels of aromatizable androgen (500-2000 ng/ml), low levels of estradiol (less than 10 ng/ml), and granulosa cells with an extant level of aromatase activity 200 times lower than that in a preovulatory follicle. Based on these biochemical criteria, healthy (luteal phase) follicles were not distinguishable from atretic follicles. Granulosa cells from the luteal phase follicles were responsive to FSH with respect to progesterone and estradiol biosynthetic activity; the aromatase system in the cells from the mid- to late luteal phase follicles was significantly more responsive to FSH than that in cells from late follicular or early luteal phase follicles (P less than 0.05). These data suggest that the number of healthy luteal phase follicles (greater than or equal to 1 mm diameter) available for subsequent preovulatory development is limited.     

Gonadotropin-sensitive progesterone production by rhesus monkey luteal cells in vitro: a function of age of the corpus luteum during the menstrual cycle.

Progesterone production in vitro, in the presence and absence of exogenous gonadotropin, was examined in suspensions of luteal cells, isolated by collagenase digestion of rhesus monkeys corpus luteum at various stages of the menstrual cycle. Cells isolated during mid-luteal phase (days 15-19) of the cycle secreted progesterone for up to 6 h in vitro. Mid-luteal phase cells were responsive to physiologic concentrations of human chorionic gonadotropin (hCG), with progesterone production significantly (P less than 0.05) enhanced by as little as 0.1 ng hCG/ml. Maximal stimulation was obtained with 100 ng hCG/ml. Both macaque chorionic gonadotropin (mCG) and human luteinizing hormone (hLH) significantly (P less than 0.01) increased progesterone production, while human follicle stimulating hormone (hFSH) did not. Under control conditions, in the presence of nutrient medium alone (no exogenous gonadotropin), the progesterone synthetic activity of mid-luteal phase cells was significantly (P less than 0.01) greater than that of cells from late luteal phase (days 22-28) of the cycle. Moreover, progesterone production by mid-luteal phase cells was consistently stimulated (P less than 0.01) by the presence of 100 ng hCG/ml, whereas late luteal phase cells were less sensitive or unresponsive to exogenous gonadotropin. The progesterone synthetic activity of luteal cells in vitro correlated positively with both the wet weight of the excised corpus luteum (r = 0.82, P less than 0.01) and the peripheral serum progesterone concentration immediately preceding luteectomy (r = 0.66, P less than 0.01). These findings suggest that freshly isolated luteal cells reflect the functional capability of the corpus luteum in vivo. It is apparent that the age of the rhesus monkey corpus luteum of the non-fertile menstrual cycle is an important factor governing luteal cell progesterone synthetic capability and luteal cell responsiveness to gonadotropin in vitro.     

Effect of reduced luteinizing hormone concentrations on corpus luteum function during the menstrual cycle of rhesus monkeys

To further define the relationship between plasma LH concentrations and progesterone secretion by the primate corpus luteum, we examined luteal function in rhesus monkeys in response to reduced LH concentrations during the luteal phase of the menstrual cycle. Five anovulatory rhesus monkeys received a pulsatile infusion of synthetic GnRH (6 micrograms/pulse; one pulse per h, iv) to restore menstrual cyclicity. During the early luteal phase (4-5 days after ovulation), the amount of GnRH administered per pulse was reduced to 1/250th or 1/750th of the standard GnRH infusion regimen. Plasma LH concentrations, determined by bioassay, were reduced by approximately 50% during cycles maintained by reduced GnRH concentrations compared with the standard GnRH dosage. Serum progesterone concentrations were maintained for 5-6 days after GnRH reduction and declined thereafter, and premature menstruations were observed in four of seven cycles maintained by the 1/250th GnRH reduction and four of six cycles maintained with the 1/750th GnRH reduction. These results are consistent with the hypothesis that luteal regression during the nonfertile menstrual cycles of primates is due primarily to an alteration in luteal cell responsiveness to LH, rather than a reduction in the gonadotropic drive to the corpus luteum per se. When plasma LH concentrations were reduced during the early luteal phase to values below those found during the onset of luteal regression in control cycles, luteal function was maintained for 5-6 days. However, as the luteal phase progressed, the reduced LH concentrations were unable to sustain progesterone secretion, and premature menses occurred in some, but not all, animals.     

Effects of different gonadotropin pulse frequencies on corpus luteum function during the menstrual cycle of rhesus monkeys

In the nonfertile menstrual cycle, the frequency of episodic LH secretion declines from approximately 1 pulse/h in the early luteal phase to 1 pulse/4-8 h in the mid- to late luteal phase, but the relevance of this phenomenon to the initiation of functional luteal regression is not completely understood. We investigated whether a reduction in LH pulse frequency causes a decline in luteal progesterone production by experimentally reducing LH pulse frequency during the early luteal phase, and measured the effects on the subsequent plasma progesterone pattern and the onset of luteal regression. Rhesus monkeys were rendered anovulatory by placing radiofrequency lesions in the arcuate region of the medial basal hypothalamus or surgically transecting the hypothalamic-pituitary stalk. Endogenous gonadotropin secretion and ovulatory menstrual cycles were restored by pulsatile infusion of synthetic GnRH at a frequency of 1 pulse/h. Commencing on days 3-6 of the luteal phase, GnRH frequency was changed to either 1 pulse/8 h (four animals) or 1 pulse/24 h (four animals), or maintained at the standard 1 pulse/h frequency (four animals). Luteal phases of 13- to 17-day duration were observed in all animals kept on the 1 pulse/h frequency and in three of four animals in which the frequency was changed to 1 pulse/8 h on day 3 of the luteal phase. Daily midluteal phase (days 5-10) plasma progesterone levels observed in response to the 1 pulse/h and 1 pulse/8 h infusion regimens were similar (mean +/- SE, 4.1 +/- 0.4 vs. 3.2 +/- 0.4 ng/ml; P greater than 0.1). In contrast, short luteal phases were observed in all animals after the LH pulse frequency was reduced to 1 pulse/24 h. Comparison of plasma LH responses to a representative GnRH pulse of each GnRH infusion regimen revealed that the maximal LH levels attained in response to 1 pulse/8 h (47.5 +/- 11.5 ng/ml) were significantly greater (P less than 0.05) than the maximal LH levels attained in response to 1 pulse/h (30.5 +/- 3.2 ng/ml) or 1 pulse/24 h (27.2 +/- 5.0 ng/ml). Progesterone levels remained elevated for 140-200 min after the LH pulse resulting from the 1 pulse/8 h infusion regimen. In response to the 1 pulse/24 h infusion regimen, plasma progesterone levels remained elevated for 60 min after the LH pulse.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prostaglandin synthesis, metabolism, and signaling potential in the rhesus macaque corpus luteum throughout the luteal phase of the menstrual cycle

Prostaglandins in the corpus luteum (CL) reportedly serve as luteotropic and luteolytic agents. Based mainly on studies conducted in domesticated animals and rodents, prostaglandin E2 (PGE2) is generally considered a luteotropic factor, whereas uterine-derived prostaglandin F2alpha (PGF2alpha) initiates luteolysis. However, the role of prostaglandins in regulating primate luteal structure-function is poorly understood. Therefore, a comprehensive analysis of individual mRNA or proteins that are involved in PGE2 and PGF2alpha biosynthesis, metabolism, and signaling was performed using CL obtained at distinct stages of the luteal life span during the menstrual cycle in rhesus monkeys. Peak levels of proteins involved in PGE2 synthesis (prostaglandin-endoperoxide synthase 2, microsomal PGE2 synthase-1) and signaling (PGE2 receptor 3) occurred during periods corresponding to development and maintenance of the primate CL. Immunohistochemistry studies indicated that large luteal cells express PGE2 synthesizing and signaling proteins. Expression of PGE2 synthesizing and signaling proteins significantly decreased preceding the period of functional regression of the CL, which also coincided with increasing levels of PGF2alpha receptor protein expression within the large luteal cells. Moreover, significant levels of mRNA expression for several aldoketo reductase family members that synthesize PGF2alpha from other prostaglandins were observed throughout the rhesus macaque luteal phase, thus supporting the possibility of intraluteal PGF2alpha production. Collectively, our results indicate that there may be intraluteal synthesis and signaling of PGE2 during development and maintenance of the primate CL, followed by a shift to intraluteal PGF2alpha synthesis and signaling as the CL nears the time of luteolysis.     

Prolactin secretion and corpus luteum function in women with luteal phase deficiency

Luteal phase deficiency (LPD) as a clinical infertility problem is considered to have a heterogeneous etiology. Hyperprolactinemia has long been considered a causative factor of LPD. In this context we investigated PRL secretion in 18 women with LPD. All of the subjects were infertile with 2 out of phase (greater than 2 days) endometrial biopsies; 10 of the women also had daily blood samples, this latter subgroup had significantly decreased integrated luteal phase progesterone (P) levels compared to normal women with in-phase biopsies. PRL secretion was investigated as follows: 1) daily blood levels; 2) pulsatile secretion patterns in 3 cycle phase [early follicular (12 h); late follicular (12 h); midluteal (24 h)], 3) LH-PRL coupling, and 4) nocturnal patterns. Results were compared to findings in 36 normal women. The mean daily levels of PRL over the menstrual cycle were not different between the two groups (LPD, 12.1 +/- 1.5; normal, 13.8 +/- 0.8 microgram/L; P = 0.3). There was no correlation between luteal phase integrated P and PRL levels for either group. There was a small difference in the PRL pulse amplitude in the early follicular phase between the LPD and normal women (2.6 +/- 0.3 vs. 5.5 +/- 1.3 micrograms/L; P less than 0.05). There were no significant differences between groups in PRL pulse frequency or mean level during the 12 or 24 h in any cycle phase. There was an equivalent amount of LH-PRL pulse coupling in both groups in all three cycle phases. Diurnal and nocturnal PRL secretion was studied by breaking the 24 h data (midluteal) into day (0700-2300 h) and night (2300-0700) segments. Mean PRL levels were higher at night in both groups (LPD, 15.9 vs. 12.6; normal, 15.4 vs. 9.3 micrograms/L; P less than 0.05), as expected. There were no differences in nocturnal PRL secretory patterns between the two groups. In summary, we have serious reservations whether abnormalities in PRL secretion are a common or integral part of the pathophysiology of LPD. From previous work we know these subtle abnormalities in PRL secretion in LPD are associated with definite abnormalities in gonadotropin secretion. We believe these gonadotropin abnormalities are probably more significant in terms of decreased P secretion.     

Human corpus luteum: luteinizing hormone and chorionic gonadotropin receptors during the menstrual cycle

To characterize and determine the concentration of LH/hCG receptors in human corpora lutea of the menstrual cycle, we measured occupied and unoccupied receptors and determined the association (Ka) and dissociation (Kd) constants individually in 23 corpora lutea (CL) and 4 corpora albicantia obtained at the time of tubal ligation from 25 normal cycling women. We found no [125I]hCG binding in any of the corpora albicantia. Scatchard plot analysis for each CL revealed a linear binding plot indicative of a single set of LH/hCG receptors. The mean concentration of unoccupied receptors was 36 +/- 10 (+/- SE) fmol/mg protein in the early luteal phase (days 15-19; n = 5), 64 +/- 11 fmol/mg protein in the midluteal phase (days 20-25; n = 13), and 42 +/- 19 fmol/mg protein in the late luteal phase (days 26-30; n = 5). The concentrations of occupied receptors were 56 +/- 8, 46 +/- 6, and 54 +/- 12 fmol/mg protein in the early, mid-, and late luteal phases, respectively. Total (occupied plus unoccupied) receptor concentrations reached maximum levels of 110 +/- 11 fmol/mg protein in the midluteal phase. Ka increased progressively from 12 +/- 4 X 10(9) mol/L-1 in the early luteal phase to 19 +/- 7 X 10(9) and 21 +/- 8 X 10(9) mol/L-1 in the mid- and late luteal phases. We conclude that in normal CL, 1) total and unoccupied LH/hCG receptor levels parallel progesterone secretion; 2) changes in the binding affinity may be important in sustaining and/or rescuing the CL; and 3) loss of LH/hCG receptors is probably related to luteolysis.     

Induction of luteal phase defects in rhesus monkeys by follicular fluid administration at the onset of the menstrual cycle

Administration of charcoal-extracted porcine follicular fluid (pFF) to rhesus monkeys on days 1-3 of the menstrual cycle suppressed serum FSH, but not LH, during the early follicular phase. Although timely midcycle gonadotropin surges occurred in 5 of 6 pFF-treated monkeys, the preovulatory rise in serum estradiol was markedly diminished and serum progesterone (P) levels were subnormal at midluteal phase. The wet weight of the corpus luteum excised from pFF-treated monkeys at midluteal phase was less than that from controls. Moreover, both basal and gonadotropin (hCG)-sensitive P production by short-term suspensions of luteal cells from pFF-treated monkeys was significantly less than that by control cells. These findings provide direct support for the concept that FSH-dependent events during the early follicular phase are important determinants of the subsequent function of the corpus luteum of the menstrual cycle. Since pFF-induced luteal dysfunction was strikingly similar to spontaneous luteal phase defects found in monkeys and women, this primate model permits study of the mechanism(s) whereby FSH deficiency during recruitment and selection of the dominant follicle portends defective luteal function and infertility in women.     

Adenylate cyclase in the corpus luteum of the rhesus monkey. III. Changes in basal and gonadotropin-sensitive activities during the luteal phase of the menstrual cycle

The activity of adenylate cyclase was examined in corpora lutea (CL) obtained from rhesus monkeys at specific stages in the luteal phase of the menstrual cycle [3-5, 6-8, 9-12, 13-15, and 16 days (menses) after the midcycle LH surge]. The conversion of [alpha-32P]ATP to [32P]cAMP was used to monitor adenylate cyclase activity. cAMP production in luteal homogenates was assessed in the absence (basal activity) and presence of maximum stimulatory doses of forskolin (100 microM), 5'-guanylylimidodiphosphate [GMP-P(NH)P; 50 microM], GTP (50 microM), and GTP plus increasing doses of hLH and hCG. Basal activity was low in the early luteal phase (days 3-5; mean +/- SE, 1.2 +/- 0.2 pmol cAMP/mg protein X min), increased (P less than 0.05) by the midluteal phase (days 6-8 and 9-12, 2.1 +/- 0.4 and 2.0 +/- 0.3 pmol/mg X min, respectively), and then declined (P less than 0.05) during the late luteal phase (days 13-15 and 16-menses, 1.6 +/- 0.3 and 1.2 +/- 0.5 pmol/mg X min, respectively). Activity stimulated by GTP and GMP-P(NH)P [e.g. GMP-P(NH)P approximately 12 times basal level] followed the same pattern as basal activity during the luteal phase. In contrast, cAMP production in the presence of forskolin did not change significantly throughout the luteal phase. In the midluteal phase (days 6-8 and 9-12; n = 12), hCG and human LH (hLH) stimulated adenylate cyclase in a similar dose-dependent manner. Maximal stimulation of cAMP production by hCG was about 10% greater (P less than 0.05) than that by hLH; the activation constant was 12.3 nM for hCG and 28.3 nM for hLH. The maximal response to hLH and hCG as well as the sensitivity of adenylate cyclase to activation by hLH were greater (P less than 0.05) in the midluteal phase than in the early or late luteal phase. Decreased basal, gonadotropin-stimulated, and guanine nucleotide-stimulated cAMP production and diminished sensitivity of adenylate cyclase to hLH correlated with a decline (P less than 0.05) in circulating progesterone and luteal weight during the late luteal phase. Thus, the adenylate cyclase system of the rhesus monkey CL undergoes significant changes during the luteal phase which are associated with the development and regression of the CL of the menstrual cycle. Mechanisms that modulate gonadotropin and nucleotide activation of adenylate cyclase without interfering directly with the catalytic unit are implicated in the changes that accompany luteolysis.     

Luteal responses to gonadotropin-releasing hormone during the luteal phase: relation to the age of corpus luteum

The pituitary and luteal responsiveness of GnRH were studied in 20 normal women at different stages of the luteal phase (LP). Blood samples were collected every 15 min for 180 min before and 120 min after the iv injection of 25 micrograms GnRH. The studies were performed in the early LP (ELP; days 2-3 of LP; n = 5), mid-LP (MLP: days 4-8 of LP; n = 11), late LP (LLP; days 9-12 of LP; n = 13), and premenstrual phase (PMP; days 13-14 of LP; n = 3). Plasma LH, FSH, progesterone (P), and estradiol (E) levels were assayed by RIA. The data were analyzed as integrated secretory area before (ISAb) and after GnRH stimulation (ISAs) and in terms of their percent increase with respect to the basal value. In all studies, GnRH elicited increases in plasma LH and FSH (P less than 0.001). On the other hand, in the ELP, GnRH did not alter steroid ISAs compared to their ISAb, while significant increases in plasma P and E levels were found in the MLP (P, P less than 0.01; E, P less than 0.02) and LLP (P and E, P less than 0.01). In the PMP, two women had no increase in steroid secretion; in the remainder of the subjects, both P and E ISAs markedly increased. This different pattern was not related to basal steroid levels. All women who had a blunted steroid response in the ELP or PMP had a normal secretory response of both P and E when studied at the other LP stages of the same cycle. Furthermore, there was a positive linear correlation between plasma P and E for the ISAb and ISAs values, while the secretory patterns of gonadotropins and steroids were not related to each other. In conclusion, the corpus luteum is able to respond to GnRH to GnRH at a well identified period of the LP. This pattern indicates variable dependence of the corpus luteum on the functional activity of the hypothalamic-pituitary axis.     

Plasma lipid and lipoprotein levels during the follicular and luteal phases of the menstrual cycle

Estrogen levels are higher during the luteal compared with the follicular phase of the menstrual cycle. It was hypothesized that the luteal compared with the follicular phase has a lipid and lipoprotein profile associated with decreased coronary heart disease (CHD) risk. This was tested using well-defined data from healthy, well-characterized premenopausal Caucasian women under very controlled metabolic conditions. The percent differences in lipid, lipoprotein, and sex hormone levels between the follicular and luteal phases were estimated using generalized estimating equations after adjusting for age, body mass index, calendar time, and season. The low-density lipoprotein cholesterol (LDL-C) level was 6.2% lower (P = 0.015), and the total cholesterol/high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratios were 5.1% (P = 0.0006) and 8.4% (P = 0.002) lower, respectively, during the luteal phase. Levels of estradiol and other estrogens were significantly higher (by>100% each; P < 0.0001 in all cases) in the luteal phase. These findings support the study hypothesis. Fluctuations in levels of LDL-C and the total cholesterol/HDL-C and LDL-C/HDL-C ratios between menstrual cycle phases need to be considered in the screening and medical monitoring of premenopausal women, especially those with borderline levels. Although small, such fluctuations may prove to be clinically significant in the long run. Studies involving premenopausal women need to more clearly define and validate menstrual cycle phase in the design and interpretation of study results.     

Luteotropic effects of prostaglandin E2 on the human corpus luteum of the menstrual cycle and early pregnancy

Human corpora lutea (CL) of the menstrual cycle and early pregnancy were excised at operation, cut into pieces, and incubated or superfused in the presence of hCG or prostaglandin (PG) E2. After incubation, the tissue levels of cAMP and the medium concentrations of progesterone (P) were determined, while the concentration of P was analyzed after superfusion. PGE2 stimulated cAMP formation in CL from all phases of the menstrual cycle as well as from early pregnancy and caused an increase in P formation in CL from the early and midluteal phases of the menstrual cycle as well as from early pregnancy. A difference was found in the latency, the lag phase until maximal response, and the duration of response between the effects of PGE2 and hCG on both cAMP and P formation. Thus, the effect of PGE2 started more rapidly and was of shorter duration than that of hCG. The stimulatory effect of PGE2 on CL from early pregnancy was of the same magnitude as that of CL from the menstrual cycle. On the other hand, hCG had less stimulatory effect on cAMP and P formation in CL from early pregnancy compared to CL from the menstrual cycle. We conclude that PGE2 stimulates P and cAMP formation in isolated human CL from all phases of the menstrual cycle as well as in early pregnancy, indicating a luteotropic effect of this PG.     

Corpus luteum response to exogenous HCG during the mid-luteal phase of the menstrual cycle

OBJECTIVE: To assess a range of exogenous HCG regimes designed to simulate the endocrine environment occurring in biochemical, single and multiple pregnancies and to study the response of the corpus luteum to those regimes. DESIGN: Prospective clinical study. PATIENTS: Twenty-five normally cycling women aged 24-35 years were given one of four regimes of HCG injections designed to mimic the HCG concentrations found following spontaneous implantation. Regimes A, B, C and D were designed with starting HCG doses of 60, 140, 250 and 1000 iu, respectively. The daily HCG injections were then increased to give a doubling concentration every 30 h for regime A, every 27 h for regime B, every 24 h for regimes C and D. HCG administration was started on either days 7 or 8 after the LH peak. MEASUREMENTS: Plasma HCG and progesterone concentrations. RESULTS: Subjects given regime A failed to demonstrate any rescue of the corpus luteum despite low-detectable amounts of HCG in the circulation equivalent to those seen in some biochemical pregnancies. In contrast, subjects given regimes B and C demonstrated prompt increases in progesterone secretion immediately after the first HCG injection achieving HCG and progesterone concentrations in plasma similar to those seen in normal singleton pregnancies. Subjects given regime D also showed rapid rescue of the corpus luteum but this time achieved plasma HCG concentrations in the range normally seen in multiple pregnancies. All subjects in regimes B, C and D secreted significantly higher amounts of progesterone than those in regime A (P<0.001). However, despite the greater amounts of HCG used in regime D, the amount of progesterone produced was not significantly different from regimes B or C. CONCLUSIONS: The exogenous HCG regimes used in this study successfully mimicked the hormonal environment found in biochemical, single and multiple pregnancies and elicited appropriate corpus luteum responses.     

Angiogenesis in the human corpus luteum: changes in expression of angiopoietins in the corpus luteum throughout the menstrual cycle and in early pregnancy

CONTEXT: Blood vessel stabilization is regulated by angiopoietins and important for angiogenesis in the corpus luteum. OBJECTIVE: To study angiogenesis and blood vessel stabilization in the human corpus luteum, changes in expression of angiopoietin (Ang)-1, Ang-2, and their specific receptor, Tie-2, together with the number of blood vessels and pericytes were examined in the corpus luteum throughout the menstrual cycle and in early pregnancy. DESIGN: The number of blood vessels and pericytes was determined by immunohistochemistry for CD34 and alpha-smooth muscle actin, respectively. Ang and Tie-2 expression were examined by immunohistochemistry or RT-PCR. RESULTS: The number of blood vessels increased during the early luteal phase, whereas the number of pericytes was small in the early luteal phase and increased in the midluteal phase, suggesting that angiogenesis is undergoing during the early luteal phase and blood vessels are stabilized in the midluteal phase. Blood vessels and pericytes decreased in number during the late luteal phase. The increased number of both blood vessels and pericytes seen in the corpus luteum of early pregnancy suggests that angiogenesis is undergoing accompanied by blood vessel stabilization. Ang-2 expression with low Ang-1 expression was found during the early luteal phase. Thereafter, increasing Ang-1 expression during the midluteal phase, declining Ang-1 expression with continued Ang-2 expression during the late luteal phase, and relatively high Ang-1 expression in early pregnancy were observed. CONCLUSIONS: The change in Ang expression is closely associated with angiogenesis, blood vessel stabilization, and blood vessel regression during the divergent phases of luteal formation, luteal regression, and luteal rescue by pregnancy.     

Receptors for lactogenic hormones in the porcine corpus luteum: properties and luteal phase concentrations

Homogenates of pig corpora lutea contained specific, high-affinity receptors for ovine prolactin (oPRL) and human GH (hGH). Specific hormone binding was enhanced by divalent metal ions, but only when included in the binding reaction. Divalent metal ions did not act by increasing the recovery of bound hormone by low-speed centrifugation, but appeared to promote the formation of a more stable hormone-receptor complex. Both oPRL and hGH tracers were bound in similar amounts and with similar affinities by pig luteal homogenates and the concentrations of either unlabelled hormone required to displace specific binding of either tracer by 50% were identical. In contrast, 125I-labelled oGH failed to bind to pig luteal homogenates and oGH competed poorly for hGH or oPRL binding. Only hormones with prolactin-like activity competed for 125I-labelled oPRL binding. Specific prolactin binding was low in recently ovulated and early luteal phase corpora lutea, increased significantly in the mid-luteal phase and declined once more in the late luteal phase. Receptor concentrations increased with increasing gestational age.     

Changes in FSH and the pulsatile secretion of LH during treatment of ewes with bovine follicular fluid throughout the luteal phase of the oestrous cycle

Treatment of Damline ewes with twice-daily i.v. injections of bovine follicular fluid during the luteal phase for 10 or 2 days before prostaglandin-induced luteolysis resulted in a delay in the onset of oestrous behaviour and a marginal increase in ovulation rate. During the treatment cycle, blood samples were withdrawn at 15-min intervals for 25 h from 08.00 h on days 1, 6 and 10 (day 0 = oestrus). At all three stages of the luteal phase, plasma FSH concentrations were suppressed relative to controls 3 h after the 09.00 h injection of follicular fluid and remained low until 06.00 h on the following day. In the 10-day treatment group LH pulse amplitude was significantly greater than that of controls on days 6 and 10. Pulse frequency remained high throughout treatment and was significantly higher relative to controls on day 10 despite normal progesterone levels. The results suggest that the higher pulsatile LH secretion during the luteal phase is due to reduced negative feedback effects of oestradiol occurring as a result of the follicular fluid-induced reduction in FSH.