Decreased Progesterone Secretion Research Articles

Synergistic effects of insulin-like growth factor I and gonadotrophins on relaxin and progesterone secretion by ageing corpora lutea of pigs.

Insulin-like growth factor I (IGF-I) is involved in paracrine/autocrine regulation of gonadal steroidogenesis and peptide hormone biosynthesis. This study was designed to determine whether IGF-I alone, or an interaction of IGF-I, is involved in augmenting the actions of luteinizing hormone (LH) and prolactin in controlling relaxin and progesterone secretion from ageing corpora lutea of hysterectomized gilts at days 110, 113 and 116 after oestrus. Luteal tissue slices were incubated for 8 h with IGF-I (0, 50, 300 ng ml-1), LH (0, 100, 1000 ng ml-1), and prolactin (0, 100, 1000 ng ml-1) alone or in combination. Progesterone and relaxin concentrations were determined by radioimmunoassay of spent medium and of homogenates from luteal tissue slices before and after incubation. Porcine luteal tissue from day 110 had a net output of 25 ng progesterone and 26 ng relaxin in the control and of 65 ng progesterone and 2125 ng relaxin in the combined IGF-I, LH and prolactin treatment mg-1 of luteal tissue, respectively. IGF-I, LH and prolactin alone or in combination significantly increased (P < 0.01) progesterone production by luteal tissue from day 110, but they were partially effective at day 113 and ineffective at day 116. By contrast, the same hormone treatments increased relaxin production by luteal tissue from days 110 and 113. Even at day 116, prolactin alone or with LH or IGF-I continued to stimulate relaxin production. In conclusion, IGF-I augments the ability of prolactin and LH to increase relaxin production by ageing corpora lutea; however, a decrease in progesterone secretion and an increase in relaxin secretion at day 113 indicate that different mechanisms control progesterone and relaxin secretion in pigs.

Formula omitted] desensitization of a high affinity PGF 2α receptor in the ovine corpus luteum

The corpus luteum (CL) of the sheep exhibits a differential sensitivity to PGF2α in vivo in terms of an increase in oxytocin (OT) secretion and a decrease in progesterone secretion, pointing to the presence in vivo of both high and low affinity receptors for PGF2α. The presence of the high affinity PGF2α receptor was assessed by monitoring the secretion rate of OT from the ovine CL in response to subluteolytic infusions of PGF2α. Rapid desensitization to PGF2α occurred after only one hour of infusion, while a minimum rest period of six hours was required to restore sensitivity. The possibility that these findings could be explained by the depletion and resynthesis of OT was excluded by demonstrating an increase in OT secretion rate with supra-physiological levels of PGF2α two hours after desensitization. Collectively, these results indicate the presence of a high affinity receptor for PGF2α in the ovine CL which exhibits desensitization and recovery in vivo . The temporal nature of the desensitization and recovery of the high affinity PGF2α receptor controlling luteal OT secretion may contribute to the pulsatile nature of PGF2α release from the ovine uterus.

The induction of premature luteolysis in normal women—follicular phase luteinizing hormone secretion and corpus luteum function in the subsequent cycle

Women with luteal phase deficiency have been shown to have an increased frequency of luteinizing hormone pulses in the early follicular phase of the menstrual cycle. Because progesterone is known to modulate luteinizing hormone secretion, it has been hypothesized that the decreased progesterone secretion in a previous luteal phase deficiency cycle could lead to the abnormal luteinizing hormone secretory pattern in the ensuing early follicular phase. With the possibility that the higher luteinizing hormone pulse frequency might lead to another deficient luteal phase, it becomes conceivable that luteal phase deficiency could be self-perpetuating. To test this hypothesis, luteal phase deficiency was induced in six normal women by decreasing luteinizing hormone support of the corpus luteum with a gonadotropin-releasing hormone antagonist Nal-Glu, administered twice daily beginning in the midluteal phase after a control cycle. During the antagonist-treated luteal phase, each subject met the predetermined criteria for induced luteal phase deficiency: a 33% or greater decrease in integrated progesterone from the control cycle and an integrated progesterone level less than 100 ng/ml per day. Luteinizing hormone secretion patterns were determined by frequent blood sampling performed every 10 minutes for 12 hours in the early follicular phase of the control cycle and the cycle after antagonist administration. Daily luteal progesterone levels were measured in the control, treatment, and posttreatment cycles. Each volunteer served as her own control. Standard parameters were compared between the control and posttreatment pulse studies in the early follicular phase: (1) luteinizing hormone pulse frequency was 9.5 +/- 1.0 vs 10.0 +/- 0.9 pulses/12 hours, control vs posttreatment, respectively, p = 0.5; (2) luteinizing hormone pulse amplitude was 11.0 +/- 1.3 vs 12.0 +/- 2.2 ng/ml, p = 0.6; and (3) luteinizing hormone mean level was 19.4 +/- 2.3 vs 22.2 +/- 3.3 ng/ml, p = 0.1. Corpus luteum function was also compared between the control and posttreatment cycles. Luteal phase length was 13.7 +/- 0.6 vs 12.7 +/- 0.6 days, p = 0.08. Integrated progesterone values were 136.9 +/- 12.9 vs 130.5 +/- 11.3 ng/ml per day, p = 0.5. Therefore no discernible abnormalities in early follicular luteinizing hormone secretions or corpus luteum secretion of progesterone occurred after an induced luteal phase deficiency cycle.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of relaxin on facilitation of parturition in dairy heifers

Purified pig relaxin (3000 U/mg) was injected i.m. into pregnant Holstein dairy heifers on Day 276 or 277 to determine its effect on parturition and sequential measurements of the pelvic area, cervical dilatation, and peripheral blood-plasma concentrations of progesterone and relaxin. Treatments included phosphate-buffer saline (2 ml, Group C, N = 7), relaxin once (1 mg, Group 1R, N = 7), and twice (2 mg, 12 h apart; Group 2R, N = 7). Intervals (mean +/- s.e.) between the first injection of relaxin or PBS and calving were 64 +/- 17, 80 +/- 19 and 125 +/- 34 h for Groups 2R, 1R and C, respectively. The calving intervals were reduced in Groups 2R (P less than 0.01) and 1R (P less than 0.05) compared with Group C. The incidence of dystocia was 29% (2 of 7) in Group 2R and 43% (3 of 7) in Group 1R compared with 57% (4 of 7) in Group C (P less than 0.01). Body weights and ratios of males to females of the calves were similar (P greater than 0.05) between groups. Progesterone plasma concentrations decreased (P less than 0.01) earlier in Groups 1R and 2R compared with Group C, and this acute decrease began within 6 h of treatment. At 24 h after relaxin or PBS injection, progesterone concentrations were 2.7 +/- 1.1 ng/ml for Group 2R, 3.5 +/- 0.9 ng/ml for Group 1R, and 6.0 +/- 0.1 ng/ml for Group C. Relaxin reached peak blood-plasma levels of 19 +/- 2.2 ng/ml 1 h after injection of relaxin, but remained unchanged, 0.3 +/- 0.01 ng/ml, in Group C. Pelvic area was increased 26%, 22% and 14% and cervical dilatation was increased 109%, 76% and 53% 48 h after injection in Groups 2R, 1R and C, respectively, but these responses were similar among groups at the time of parturition. We conclude that two i.m. injections of relaxin facilitated earlier calving, acutely decreased progesterone secretion, increased cervical dilatation and pelvic area expansion, and decreased the incidence of dystocia in dairy heifers.

Abrupt Shifts in Relaxin and Progesterone Secretion by Aging Luteal Cells: Luteotropic Response in Hysterectomized and Pregnant Pigs*

Although a prominent role of conceptuses in the hormonal control of normal parturition in the pig is well founded, mechanisms are entrained that cause a timed relaxin release and an abrupt decrease in progesterone secretion in the complete absence of the uterus. This study focused on the steroidogenic and peptide hormone secretory capacities of aging porcine luteal cells in culture on specific days during a narrow window (days 110-116) when abrupt shifts occur in their function. Dispersed luteal cells (3 x 10(5) cells/well) from hysterectomized and pregnant gilts on days 110, 113, and 116 after estrus were cultured for 24 h with porcine (p) LH, pPRL, prostaglandin E1 (PGE1), PGE2, and (Bu)2cAMP. Progesterone and relaxin concentrations in cells preceding culture and in the spent medium were quantified by RIA. Progesterone in cells before culture was less (P less than 0.05) than that released into the medium, while relaxin levels were greater (P less than 0.05) than those in the medium. Relaxin stored in luteal cells of hysterectomized gilts was consistently greater (P less than 0.01) than that during the same days of late pregnancy; however, progesterone was greater (P less than 0.01) in hysterectomized compared with pregnant gilts only on day 116. Relaxin release was greater (P less than 0.01) in hysterectomized compared with pregnant gilts on days 113 and 116, whereas progesterone was greater (P less than 0.05) on days 110 and 116 in hysterectomized compared with pregnant animals. pLH, pPRL, and (Bu)2cAMP increased (P less than 0.05) relaxin secretion in hysterectomized gilts on days 110, 113, and 116, but only on day 110 in pregnant animals. These hormones consistently increased (P less than 0.05) progesterone release only on day 110 in both groups of gilts. PGE1 increased (P less than 0.01) relaxin release in hysterectomized, but not pregnant, gilts; it was not effective in altering progesterone in either group. PGE2 increased the release of both hormones on day 113 in both groups. The percentage of large cells (i.e. greater than 20 microns in diameter) was consistently greater (P less than 0.01) on days 110-116 in hysterectomized compared with pregnant gilts. Both luteal cell relaxin concentrations and the population of electron-dense granules decreased from days 110-116 in pregnant, but not in hysterectomized, gilts; luteal cells from postpartum animals were nearly depleted of granules, and empty vesicles were prominent. The secretory response of the cells to tropic hormone stimulation is preprogrammed from the previous estrus that occurred more than 110 days previously.(ABSTRACT TRUNCATED AT 400 WORDS)

Gonadotropin-releasing hormone inhibition of LH stimulated progesterone secretion by porcine granulosa cells in vitro

GnRH has several direct actions on rat granulosa cells. Specific receptors for GnRH have been demonstrated on rat and human ovaries. Whether the porcine ovary has specific receptors for GnRH is still debated and the physiological actions of GnRH on porcine granulosa cells have not yet been clarified. Consequently, we have examined the actions of a GnRH agonist (GnRHa) on basal and LH stimulated progesterone secretion by porcine granulosa cells. GnRHa inhibited both basal and LH stimulated progesterone secretion by granulosa cells from medium (3–5 mm) and large (6–10 mm) antral follicles during 3 day incubations. LH stimulated progesterone secretion was more sensitive to inhibition than basal progesterone secretion. Studies on the time course for GnRHa inhibition of progesterone secretion indicated that the decrease in progesterone secretion occurred 48 to 72 hr after first exposure to GnRHa. Earlier inhibition occurred in only a fraction of the experiments. GnRHa did not have to be present during the time when inhibition occurred. Incubations of 2 days with GnRHa were just as effective as 3 day incubations at inhibiting progesterone secretion on day 3. Furthermore, a 30 min exposure to GnRHa on day 1 was just as inhibitory as a full 2 day incubation with GnRHa in inhibiting LH stimulated progesterone secretion on day 3. Incubation of the cells for 3 days prior to exposure of the cells to GnRHa did not alter the time course for GnRHa action. GnRHa did not alter the DNA content of the cultures in up to 6 day incubations or the number of viable cells attached to the wells in up to 3 day incubations. These studies suggest that an ovarian GnRH-like molecule could play a role in decreasing the responsiveness of particular follicles to LH and thus contribute to atresia.

Shortening of luteal phase in common marmosets by sheep ovarian follicular fluid peptide

A low molecular weight peptide has been partially purified from sheep follicular fluid. It inhibited FSH binding to granulosa cells from ovarian follicles of common marmosets ( Callithrix jacchus ). When injected into cycling marmosets during the follicular phase, it reduced the area under the curve (AUC) of circulating progesterone. The peptide also shortened the luteal phase in all marmosets during the treatment cycle compared to the pretreatment control cycle. These results indicate that the ovarian follicular fluid peptide inhibited FSH binding to granulosa cells thereby probably resulting in decreased progesterone secretion (AUC) from these cells and subsequently inducing luteal insufficiency.

Prostaglandin F2 alpha-stimulated release of ovarian oxytocin in the sheep in vivo: threshold and dose dependency.

To determine the threshold of prostaglandin F2 alpha (PGF2 alpha)-stimulated oxytocin secretion from the ovine corpus luteum, low levels of PGF2 alpha (5-100 pg/min) were infused into the ovarian arterial blood supply of sheep with ovarian autotransplants. PGF2 alpha was infused for six sequential 10-min periods at hourly intervals, 6, 12, or 24 days after estrus (n = 3 for each day). Each cycle day was studied during a separate cycle. Oxytocin and progesterone in ovarian venous and carotid arterial plasma was measured by radioimmunoassay, and secretion rates were determined (venous-arterial concentration x plasma flow). In animals treated on Day 6, 5 pg/min PGF2 alpha caused a significant release of oxytocin (p less than 0.01), whereas in animals treated on Day 12, this threshold was 40 pg/min (p less than 0.05). In animals treated on Day 24, the threshold for oxytocin release was greater than 100 pg/min. PGF2 alpha did not significantly change ovarian blood flow or progesterone secretion rate on any day (p greater than 0.05). To determine residual luteal oxytocin after each threshold experiment, 5 mg PGF2 alpha was given i.m. to all animals. Significantly more oxytocin was released by Day 6 than by Day 12 and Day 24 corpora lutea, and by Day 12 than by Day 24 corpora lutea (1.2 micrograms, 0.7 microgram, and 0.3 microgram, respectively; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibitory effect of oxytocin and vasopressin on steroid release by cultured porcine luteal cells.

Previously, we have demonstrated the presence of substances reacting like arginine vasopressin (AVP) and oxytocin (OXT) in acid extracts of corpora lutea (CL) of pigs by RIA. The present study examined purified extracts of CL by using HPLC. The results of these experiments show that CL of nonpregnant sows contain AVP and OXT. Little is known about possible auto- and paracrine effects of AVP and OXT in the ovary. Therefore, we investigated the influence of AVP and OXT on progesterone, estradiol, and androstenedione secretion in porcine luteal cell cultures from nonpregnant sows. Progesterone and androstenedione secretion increased significantly (P less than 0.05) in the presence of ovine LH (oLH), whereas no change in basal estradiol levels could be observed under the same conditions. When AVP or OXT was added to the culture system a dose-dependent inhibition of basal as well as oLH-stimulated progesterone secretion was measured. Under basal conditions, a dose of 1 pg AVP/ml decreased progesterone secretion significantly (P less than 0.05), but to reach the same effect in the presence of OXT a dose of 100 ng/ml was necessary. In the presence of oLH the addition of as little as 0.01 pg AVP/ml inhibited progesterone secretion significantly (P less than 0.05). On the other hand, 10 ng OXT/ml or higher doses were needed to decrease oLH-stimulated progesterone release. In the presence of specific peptide antagonists the inhibitory effect on progesterone release was abolished. These results suggest that AVP and OXT effects are mediated through specific receptors. OXT and AVP also inhibited androstenedione secretion, but had no effect on estradiol secretion. Calculation of the ED50 data from dose-response curves of both peptides show that AVP is about 10(4)-fold more active than OXT in inhibiting in vitro progesterone and androstenedione secretion. This suggests that AVP as well as OXT may play an important role in the regulation of ovarian function.

Progesterone secretion as affected by 17 beta-estradiol after hysterectomy in the pig.

Serum levels of progesterone in hysterectomized gilts were determined to evaluate the effects of exogenous 17 beta-estradiol (17 beta-E2) on the secretory activity of aging corpora lutea. Gilts were hysterectomized on day 6 of the estrous cycle and given im injections of 17 beta-E2 to mimic blood levels of endogenous estrogen during normal pregnancy. Serum progesterone was determined every third or sixth day, and estrone and 17 beta-E2 were measured at 12-day intervals from days 42-192. Progesterone decreased (P less than 0.01) after day 104 in hysterectomized gilts given sesame oil. Exogenous estrogen consistently decreased (P less than 0.02) progesterone secretion during an extended period (days 45-108) in aging corpora lutea of hysterectomized gilts. Abrupt decreases in estrone, 17 beta-E2, and progesterone levels occurred after termination of estrogen injections on day 114. The decrease in the secretion of these steroids in hysterectomized gilts was similar to that observed in previous studies at parturition and during the early postpartum period. Estrogen treatment beyond day 114 inhibits follicular growth and suppresses ovulation, but behavioral estrus was induced during the terminal stages of luteal activity. In the absence of the uterus, aging corpora lutea respond to exogenous estrogen by decreased progesterone secretion, which is similar to that observed during normal pregnancy in the pig.

Alterations in the cellular membranes of regressing rat corpora lutea.

Wide angle x-ray diffraction and fluorescence polarization were used to determine the structural properties of membranes from rat luteal cells. Examination of a plasma membrane fraction by x-ray diffraction revealed a significant increase in the gel phase melting temperature during luteal regression. The membrane fluidity of this fraction as well as that of a preparation of microsomes was also studied by fluorescence polarization. Using a fluorescent probe, membrane fluidity was observed to decrease during luteolysis. The temporal correlation between structural changes in the membrane and decreased progesterone secretion suggests that alterations in the physical properties of cellular membranes may be involved in the process of luteal cell regression.

Adrenal-gonad interactions in cattle. Corpus luteum function in intact and adrenalectomized heifers.

To determine the effect of the hyperadrenal state on corpus luteum (CL) function, we treated intact and adrenalectomized (ADRX) heifers with adrenocorticotropin (ACTH) and hydrocortisone. ACTH treatment of intact heifers by infusion of 1 mg alpha 1-24 ACTH/24 hr from day 2 to 25 of an estrous cycle increased progesterone concentrations in plasma to 4 +/- .52 ng/ml plasma on days 3 to 4. Thereafter, progesterone concentrations declined, indicating severe suppression of CL function as compared to that of control heifers. Similar infusions of ACTH to ADRX heifers did not alter CL function as reflected by progesterone concentrations in jugular plasma. Infusion of ADRX animals with hydrocortisone succinate (100 mg/24 hr) decreased progesterone in plasma during the cycle, with maximum values averaging less than 4 ng/ml, compared to concentrations of 6 to 7 ng/ml in control ADRX heifers. Chronic administration of ACTH or hydrocortisone to heifers caused a decreased progesterone secretion during the luteal phase of the estrous cycle. On the basis of these results, we suggest that stress, as indicated by the hyperadrenal state, could inhibit progesterone secretion by the corpus luteum.

Mechanism of luteolysis: Effect of estradiol and prostaglandin F2α on corpus luteum luteinizing hormone/human chorionic gonadotropin receptors and cyclic nucleotides in the rhesus monkey

Recent studies from our laboratory suggest that estrogen-induced luteolysis in the primate may be mediated through intraovarian synthesis of prostaglandin F2α (PGF2α). To elucidate further the mechanism of luteolysis, normally cycling rhesus monkeys received intra-corpus luteum (CL) injections of estradiol (100 μg), PGF2α (500 μg), or the appropriate vehicles on the seventh day after the preovulatory estradiol surge. Peripheral vein blood was drawn at 30-minute intervals for 6 hours for progesterone and luteinizing hormone (LH) assays. Five hours after intra-CL injection, the CL was excised and the LH/human chorionic gonadotropin (hCG) receptor-binding activity and cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) were measured. PGF2α significantly (p < 0.05) lowered progesterone within 1 hour, while the time required for estradiol to lower progesterone significantly was 3.5 hours; there was no significant change in LH. Estradiol and PGF2α significantly (p < 0.05) decreased the LH receptor-binding capacity at 5 hours, without any change in the binding affinity. Also, PGF2α significantly (p < 0.05) increased cGMP in the CL, while cAMP remained unchanged; estradiol treatment resulted in a significant (p < 0.05) increase in cAMP with no change in cGMP. This study suggests that estradiol and PGF2α cause a decrease in progesterone secretion by a loss of the LH/hCG receptor and the PGF2α may act further through the cGMP system.

Age-related temporal changes of levels of circulating progesterone in repeatedly pseudopregnant rats.

Plasma concentrations of progesterone were measured by radioimmunoassay in spontaneous (old) and induced (young adult) repeatedly pseudopregnant rats. Mean duration of pseudopregnancy was significantly longer at 24 months of age (17.3 ± 0.5 days) than at 10 months (14.0 ± 0.3 days). In both young adult and old rats progesterone concentrations showed tniphasic patterns of change throughout pseudopregnancy with an elevated plateau seen during Days 3-8 and 3-9, respectively, in agreement with the longer duration of the luteal phase in old rats.There was little indication of any gross age-related deficiencies in progesterone levels and the patterns of their changes during pseudopregnancy of old rats. However, a two-way analysis of variance demonstrated a low grade impairment in progesterone plateau values of old rats. The significance of this deficit in terms of decreased progesterone secretion is discussed. Middle-aged rats held an intermediate position for progesterone concentrations, suggesting an age-related evolution in this type of senile deviation of the ovarian cycle.

Regulation of progesterone secretion by LH and prolactin during the first half of pregnancy in the mouse.

Pregnant mice were treated with antiserum to LH or bromocriptine to inhibit the activity of LH and prolactin, respectively. Luteal function was monitored by the radioimmunoassay of plasma progesterone. Bromocriptine treatment on Days 2 or 5 of pregnancy produced a rapid decrease in progesterone secretion, but had no effect on luteal function when given on Days 6, 7 or 8 of gestation. Treatment with LH antiserum before implantation did not inhibit progesterone secretion, but luteal function was severely impaired when the antiserum was given on Days 5--9 of pregnancy. These results demonstrate the dynamic nature of luteal dependency on prolactin and LH, and indicate that LH is an essential component of the luetotrophic complex of the mouse.

Serum hormone levels during a post-implantation LH-RH induced luteolysis in the rat

Daily administration of LH-RH (100 μg sc at 0900 and 1500 h) to rats over day 7–12 (D 7–12) of pregnancy induced reovulation by D 9 and a sustained decrease in uterine:fetal weight and vaginal bleeding by 0600 h on d 10 of pregnancy. Serum hormone levels determined at 0600, 1200, and 2000 h over D 7–12 of pregnancy revealed that luteinizing hormone (LH) was significantly elevated after each administration of LH-RH, while prolactin (PRL) was not significantly altered in any systematic fashion. An acute decline in serum progesterone at 2000 h on D 7–9 following LH-RH administration was not sustained until after 0600 h on d 10 when serum 20α-dihydroprogesterone (20α-hydroxy-4-pregnen-3-one, 20α-DHP) in LH-RH treated animals rose significantly above control (2000 h, D 10) and remained elevated throughout D 11–12. Progesterone and 20α-DHP values were reflected morpnologically after D 10 as the corpora lutea of LH-RH treated rats underwent Iuteolysis. A peak in serum estradiol levels in control animals was observed at 0600 h on Dg. Serum estradiol-17β levels in LH-RH treated animals were similar to control except at 2000 h on d 8 and D 12 when LH-RH induced a significant increase. These observations suggest that subsequent to implantation in the rat, the temporal sequence of a decrease in progesterone secretion, Iuteolysis and pregnancy failure in response to LH-RH does not result from an increase in estradiol secretion attendant to reovulation.

Mechanism of the rapid antigonadotropic action of prostaglandins in cultured luteal cells

A reproducible method for dissociation and culture of rat luteal cells is described. The concentration of LH required to produce half-maximal stimulation of progesterone secretion was 50 ng/ml. The effects of prostaglandin E(2) (PGE(2)) and prostaglandin F(2alpha) (PGF(2alpha)) on basal and luteinizing hormone (LH)-stimulated progesterone production were examined. Both prostaglandins stimulated basal progesterone production but PGE(2) was about twice as active, showing a 2-fold maximal stimulation at 0.75 muM. When either prostaglandin was incubated simultaneously with LH, a dose-dependent inhibition of progesterone secretion occurred; PGF(2alpha) was 4 times more active than PGE(2), showing 50% inhibition at a concentration of 40 x nM. Thus, both prostaglandins are more active as antagonists than as agonists of LH with respect to progesterone secretion. PGF(2alpha) also inhibited LH-stimulated adenylate cyclase activity and cyclic AMP accumulation. The block in progesterone secretion was reversed by addition of dibutyryl cyclic AMP (1 mM) but not by theophylline (5 mM) alone. These data and the finding that PGF(2alpha) did not affect the specific binding activity of the LH receptor in intact luteal cells indicate that the rapid action of prostaglandins in luteal cells is due to a block of LH-dependent production of cyclic AMP which results in a decrease in progesterone secretion.

Progesterone secretion by the corpus luteum of the early pregnant pig during superfusion in vitro with PGF-2alpha, LH and oestradiol.

Corpora lutea obtained from pregnant sows (Days 18-22) were superfused in vitro for 2-4 h with PGF-2alpha and for 3 h with LH or oestradiol or combinations of PGF-2alpha with LH or oestradiol. LH but not oestradiol stimulated progesterone secretion while superfusion for a minimum of 3 h with PGF-2alpha caused an irreversible decrease in progesterone secretion. LH and PGF-2alpha were mutually antagonistic while oestradiol did not inhibit the luteolytic action of PGF-2alpha.

Plasma steroid and gonadotrophin profiles in ovulatory but infertile women.

A group of twelve patients with a history of infertility lasting at least 2 years despite evidence of regular ovulatory cycles, were selected from an Infertility Clinic after thorough investigation had revealed no other obvious cause for their infertility. Daily plasma gonadotrophin and steroid concentrations were measured in twenty cycles from these women and the results compared with the hormonal profiles obtained from a group of eleven control 'normal' women. No significant differences were found in the concentrations of LH, FSH or oestradiol although plasma progesterone concentrations were significantly lower in the infertile women, particularly during the first half of the luteal phase. In the absence of any other demonstrable defect, it was assumed that the decreased progesterone secretion was directly or indirectly implicated in the pathogenesis of their infertility, and a number of therapeutic regimes (progesterone supplementation of the luteal phase or additional stimulation by either anti-oestrogens or exogenous gonadotrophins) were assessed for their efficacy in correcting this defect. Although plasma progesterone concentrations after most of these regimes were significantly increased, none of the patients in this series conceived.

The rat estrous cycle associated with functional corpora lutea and the mechanism of its recurrence.

Pseudopregnancy (PSP)-like cycles characterized by a fully functional luteal phase and comparable in length to the period of pseudopregnancy have been induced in normally cycling rats by the isografting of anterior pituitary (AP) implants beneath the kidney capsule. Hormonal factors associated with the induction and maintenance of these spontaneously recurring PSP-like cycles were studied by measuring blood levels of prolactin, LH, FSH, estradiol-17β, progesterone and 20α-dihydroprogesterone. Transplantation of isografts comprising 1/4 anterior pituitary extended the length of the diestrous period approximately to that of normal pseudopregnancy. However, over a range of tissue mass extending from 1/4 to 2 glands, a significant correlation was observed between the duration of diestrus and the quantity of anterior pituitary tissue employed. More than 2 glands did not further extend the length of the luteal period. The secretory patterns of progesterone and 20α-dihydroprogesterone in ovarian vein blood during the PSP-like cycle were similar to those of normal pseudopregnancy. Within limits, the progesterone concentration varied directly with the quantity of transplanted pituitary tissue. Prolactin levels measured either in serum or in the in situ pituitary did not fluctuate during the luteal phase of the PSP-like cycle; however, the magnitude of the serum prolactin concentration was directly correlated with the quantity of pituitary tissue implanted possibly reflecting a direct contribution of the implant to the circulating hormone level. It is assumed that the prolactin supply from the isograft was responsible for induction and maintenance of the PSP-like cycle, since premature termination resulted from early ergocornine injection and/or removal of the grafted pituitary tissue. However, completion of the PSP-like cycle following removal of the AP-graft on or after day 5 demonstrating the capacity of the in situ pituitary to secrete adequate prolactin for maintenance. When animals were hypophysectomized during the first half of the PSP-like cycle, the isografted pituitary being left in place, progesterone secretion increased significantly providing evidence of a suppressive action on ovarian progesterone secretion by the in situ pituitary. Hypophysectomy performed during the second half of the PSP-like cycle resulted in a decreased progesterone secretion suggesting a change in luteal responsiveness to luteotrophic stimulation taking place at midcycle. The initiator of this qualitative change in luteal function probably resides in the in situ pituitary. The circulating levels of FSH and LH did not fluctuate from basal levels; however, ovarian vein estradiol-17β increased gradually during the second half of the PSP-like cycle. It is supposed that the rising estradiol level eventually triggered gonadotrophin release on the subsequent proestrus which was required for recurrence of the cycle.Finally, a statistically significant prolongation of the PSP-like cycle was induced by bilateral hysterectomy, this prolongation being of greater length when hysterectomy was performed prior to the 9th day.