Effects of an LH-releasing hormone antagonist on the secretion of LH, FSH, prolactin and ovarian steroids at different stages of the luteal phase in the stumptailed macaque (Macaca arctoides)

1986 ◽  
Vol 111 (1) ◽  
pp. 83-90 ◽  
Author(s):  
H. M. Fraser ◽  
M. Abbott ◽  
N. C. Laird ◽  
A. S. McNeilly ◽  
J. J. Nestor ◽  
...  

ABSTRACT The role of the pituitary gonadotrophins in controlling luteal function in the stumptailed macaque has been investigated by examining profiles of serum concentrations of LH, FSH, progesterone and oestradiol in daily blood samples from 13 monkeys during the menstrual cycle, and in blood samples taken at hourly intervals between 09.00 and 21.00 h on different days of the luteal phase in 13 cycles. The effects of acute withdrawal of gonadotrophins was investigated by administering a single injection of 300 μg LHRH antagonist/kg body weight at different stages of the luteal phase during 28 cycles. Although there were high basal values and marked fluctuations of bioactive LH during the first 4 days after the LH peak, progesterone profiles showed no corresponding short-term changes, there being a slow and steady rise in progesterone concentrations during the sampling periods. After day 5, basal LH secretion decreased, but high amplitude LH pulses were identified which were associated with episodes of progesterone secretion. Administration of the LHRH antagonist caused a suppression of bioactive LH and progesterone concentrations at all stages of the luteal phase, although some basal secretion of progesterone was maintained through the 24-h period of effective antagonist gonadotroph blockade. Luteal function recovered apparently normally in all monkeys treated in the early–mid-luteal phase. Serum concentrations of FSH and oestradiol fluctuated comparatively less during the 12-h sampling periods, and the antagonist had less suppressive effects on the concentrations of these hormones. The LHRH antagonist had no apparent effect on prolactin release. It appears that the corpus luteum is relatively unresponsive to the high serum LH concentrations during the early luteal phase, but that responsiveness increases as the corpus luteum develops. The corpus luteum is, however, susceptible to withdrawal of LH not only in the mid–late luteal phase when the relationship with LH is apparent, but also during the early luteal phase. J. Endocr. (1986) 111, 83–90

1991 ◽  
Vol 128 (1) ◽  
pp. 107-113 ◽  
Author(s):  
K. B. Smith ◽  
H. M. Fraser

ABSTRACT We investigated the temporal relationship between serum concentrations of progesterone and immuno-reactive inhibin after treatment with an LHRH antagonist ([N-Ac-d-Nal(2)1,d-pCl-Phe2,d-Trp3,d-hArg(Et2)6,d-Ala10]-LHRH), during the mid-luteal phase in the macaque. Further, in an attempt to obtain a model of transitory suppression of luteal function, the effect of treatment with the LHRH antagonist for 1, 2 or 3 days during the mid-luteal phase on serum concentrations of progesterone and immunoreactive inhibin was compared. Differences in the pattern of decline of the two hormones were observed. Progesterone concentrations fell by 6 h after antagonist administration while inhibin was not significantly suppressed until 48 h. Treatment with three injections of LHRH antagonist caused a sustained suppression of luteal function as shown by low serum concentrations of progesterone and inhibin. Recovery of progesterone and inhibin secretion was observed in two out of six macaques treated with two injections of antagonist and in three out of six treated with a single injection. Therefore, with the regimens of LHRH antagonist which we employed this approach was not conducive to obtaining a reliable transitory suppression of luteal function. To elucidate further the gonadotrophin control of inhibin, six macaques were treated with three injections of the LHRH antagonist to induce a permanent suppression of luteal function but received concomitantly either human chorionic gonadotrophin (hCG) or human FSH daily for 5 days (n = 3 per group). FSH failed to prevent the antagonist-induced fall in progesterone and inhibin while hCG treatment completely reversed the inhibitory effects of the LHRH antagonist. These results give further support to the concept that the secretion of inhibin, like progesterone, is integrated with the LH control of the corpus luteum. The slower decline in inhibin after LHRH antagonist suggests that the gonadotrophic stimulus to the corpus luteum results in a more prolonged stimulus for inhibin than for progesterone secretion, or that inhibin has a longer metabolic clearance rate. Journal of Endocrinology (1991) 128, 107–113


1985 ◽  
Vol 104 (2) ◽  
pp. R1-R4 ◽  
Author(s):  
H.M. Fraser ◽  
D.T. Baird ◽  
G.I. McRae ◽  
J.J. Nestor ◽  
B.H. Vickery

ABSTRACT The dependence of progesterone secretion from the corpus luteum on pituitary gonadotrophin was examined in the cyclic stumptailed macaque by studying the effects of a single s.c. injection of a potent LH releasing hormone (LHRH) antagonist, [N–Ac–D–Nal(2)1, D–pCl–phe2, D–Trp3, D–hArg(Et2)6, D–Ala10] LHRH. A dose of 100 μg antagonist/kg administered on days 9/10 of the luteal phase in three monkeys caused a marked temporary suppression of serum concentrations of LH and progesterone during the following 32 h but levels still remained detectable and after 2 days serum hormone concentrations returned to the normal luteal-phase range. When the same animals were treated with 300 μg antagonist/kg at the same period during a subsequent cycle, serum LH levels were close to or at the limits of detection of the bioassay for the next 48 h and progesterone concentrations declined steadily, reaching non-detectable values by 48 h. In two monkeys the progesterone levels remained suppressed and they menstruated prematurely; in the third monkey the progesterone concentration rose to just above baseline and menstruation occurred at the expected time. Administration of 300μg antagonist/ kg on days 6/7 of the luteal phase in a further three monkeys also suppressed progesterone concentrations but not to baseline values, and after 2 days a normal progesterone profile was regained. These results suggest that the corpus luteum of the stumptailed macaque is largely dependent on pituitary gonadotrophin support during the mid to late luteal phase.


1992 ◽  
Vol 133 (3) ◽  
pp. 341-NP ◽  
Author(s):  
H. M. Fraser ◽  
K. B. Smith ◽  
S. F. Lunn ◽  
G. M. Cowen ◽  
K. Morris ◽  
...  

ABSTRACT The putative endocrine role of inhibin in the control of FSH secretion during the luteal phase in the primate was investigated by immunoneutralization. Antisera against the 1–23 amino acid sequence of the N-terminus of the human inhibin α subunit were raised in a ewe and three macaques. Antisera (10–20 ml) were administered to macaques on day 8/9 of the luteal phase and serum samples collected during the treatment cycle and post-treatment cycle for determination of FSH, oestradiol and progesterone. In addition, localization of inhibin within the macaque ovary at this stage of the luteal phase was investigated using the ovine antiserum. Intense immunostaining was localized within the granulosa-lutein cells of the corpus luteum with absence of staining in the thecalutein cells or other ovarian compartments. Administration of antisera was without significant effect on serum concentrations of FSH when compared with control animals, either during the first 24 h of detailed observation or for the following 10-day period of the late luteal phase and subsequent early follicular phase. These results provide further evidence that the corpus luteum is the major source of inhibin immunoreactivity during the primate menstrual cycle, but fail to support an endocrine role for inhibin in the suppression of FSH secretion. Journal of Endocrinology (1992) 133, 341–347


Reproduction ◽  
2001 ◽  
pp. 643-648 ◽  
Author(s):  
A Shaham-Albalancy ◽  
Y Folman ◽  
M Kaim ◽  
M Rosenberg ◽  
D Wolfenson

Low progesterone concentrations during the bovine oestrous cycle induce enhanced responsiveness to oxytocin challenge late in the luteal phase of the same cycle. The delayed effect of low progesterone concentrations during one oestrous cycle on uterine PGF(2alpha) secretion after oxytocin challenge on day 15 or 16 of the subsequent cycle was studied by measuring the concentrations of the major PGF(2alpha) metabolite (13,14-dihydro-15-keto PGF(2alpha); PGFM) in plasma. Two experiments were conducted, differing in the type of progesterone treatment and in the shape of the low progesterone concentration curves. In Expt 1, progesterone supplementation with intravaginal progesterone inserts, with or without an active corpus luteum, was used to obtain high, or low and constant plasma progesterone concentrations, respectively. In Expt 2, untreated cows, representing high progesterone treatment, were compared with cows that had low but increasing plasma progesterone concentrations that were achieved by manipulating endogenous progesterone secretion of the corpus luteum. Neither experiment revealed any differences in plasma progesterone concentrations between the high and low progesterone groups in the subsequent oestrous cycle. In both experiments, both groups had similar basal concentrations of PGFM on day 15 (Expt 1) or 16 (Expt 2) of the subsequent oestrous cycle, 18 days after progesterone treatments had ended. In both experiments, the increases in PGFM concentrations in the low progesterone groups after an oxytocin challenge were markedly higher than in the high progesterone groups. These results indicate that low progesterone concentrations during an oestrous cycle have a delayed stimulatory effect on uterine responsiveness to oxytocin during the late luteal phase of the subsequent cycle. This resulting increase in PGF(2alpha) secretion may interfere with luteal maintenance during the early stages of pregnancy.


1975 ◽  
Vol 79 (2) ◽  
pp. 329-336 ◽  
Author(s):  
F. Lehmann ◽  
I. Just-Nastansky ◽  
B. Behrendt ◽  
P.-J. Czygan ◽  
G. Bettendorf

ABSTRACT The effect of orally given diethylstilboestroldiphosphate (DES) and 17α-ethinyl-oestradiol-3-methylether (EEM) on plasma progesterone levels was studied. Both compounds were administered for 5 days to 5 women in daily doses of 60 mg (DES) and 30 mg (EEM). The fully informed volunteers were found to have a normal menstrual cycle before the study. The mean corpus luteum phase (corpus luteum phase = days between LH surge and onset of menstruation) of all control cycles lasted 12.8 days. Daily plasma samples were collected for radioimmunoassay (RIA) of progesterone, immunoreactive oestrogens and LH. After a control cycle the first treatment was carried out with DES. The third and the fifth cycle were control cycles again. The EEM-treatment was done in the fourth cycle. Although the effect of the two compounds was different, a dependence of the age of the corpus luteum (CL) could be demonstrated for both. DES-treatment lowered plasma progesterone levels during administration. This effect was only demonstrable if the treatment was begun on the day of the LH-peak. The length of the CL-phase remained unaltered. EEM-treatment if started on the day of the LH surge, suppressed corpus luteum function in the late luteal phase. If the treatment was started later, the effect was less pronounced. The administration of both compounds did not shorten the time between ovulation and the next bleeding. After DES-treatment this interval was not altered. After EEM-treatment the subsequent bleeding was even delayed depending on slowly decreasing levels of plasma oestrogens.


1977 ◽  
Vol 73 (1) ◽  
pp. 115-122 ◽  
Author(s):  
I. A. SWANSTON ◽  
K. P. McNATTY ◽  
D. T. BAIRD

SUMMARY The concentration of prostaglandin F2α (PGF2α), progesterone, pregnenolone, oestradiol-17β, oestrone, androstenedione and testosterone was measured in corpora lutea obtained from 40 women at various stages of the menstrual cycle. The concentration of PGF2α was significantly higher in corpora lutea immediately after ovulation (26·7 ± 3·9 (s.e.m.) ng/g, P < 0·005) and in corpora albicantia (16·3 ± 3·3 ng/g, P < 0·005) than at any other time during the luteal phase. There was no correlation between the concentration of PGF2α and that of any steroid. The progesterone concentration was highest in corpora lutea just after ovulation (24·9 ± 6·7 μg/g) and in early luteal groups (25·7 ± 6·8 μg/g) but declined significantly (P < 0·05) to its lowest level in corpora albicantia (1·82 ± 0·66 μg/g). The concentration of oestradiol-17β in the corpus luteum and luteal weight were significantly greater during the mid-luteal phase than at any other stage (concentration 282 ± 43 ng/g, P < 0·05; weight 1·86 ± 0·18 g, P < 0·005). The results indicate that regression of the human corpus luteum is not caused by a rise in the ovarian concentration of PGF2α in the late luteal phase of the cycle.


2012 ◽  
Vol 87 (Suppl_1) ◽  
pp. 49-49
Author(s):  
Cecily V. Bishop ◽  
Theodore A. Molskness ◽  
Jon D. Hennebold ◽  
Richard L. Stouffer

1996 ◽  
Vol 150 (1) ◽  
pp. 93-98 ◽  
Author(s):  
Y Nakamura ◽  
H Tamura ◽  
M Ono ◽  
K Shimamura ◽  
N Sugino ◽  
...  

Abstract The purpose of this study was to examine the possible mechanism through which RU486 induces luteolysis during the late-luteal phase in pseudopregnant (PSP) rats. PSP rats received a subcutaneous injection of RU486 in sesame oil (5 mg/kg body weight) or sesame oil alone once a day between day 9 and day 11 of pseudopregnancy. Serial blood samples were collected on days 5, 9, 10, 11 and 12 and assayed for progesterone content. To examine the possible action of RU486 through a uterine and/or a pituitary (prolactin-dependent) mechanism, PSP rats and chronic hysterectomized PSP rats which had been hysterectomized before PSP induction received a subcutaneous injection of RU486 in sesame oil (5 mg/kg body weight), sesame oil alone, prolactin in 50% polyvinylpyrrolidone (15 IU/day), or RU486 and prolactin once a day between day 9 and day 11 of pseudopregnancy. Serial blood samples were collected on days 5, 9, 10 and 11 and assayed for progesterone content. Blood samples were also collected at 0400 h on day 12 and used for prolactin and progesterone determinations. To examine the direct effect of RU486 on corpus luteum and/or pituitary, hysterectomized rats underwent hypophysectomy and pituitary autotransplantation on dioestrus 1 and received a subcutaneous injection of RU486 in sesame oil or sesame oil alone for 3 days between day 21 and day 23 after surgery. Serial blood samples were collected on days 10, 21, 22, 23 and 24 and assayed for progesterone and prolactin contents. In ordinary PSP rats, serum progesterone levels were significantly (P<0·01) lower in the RU486-treated group than in the control group (9 ± 1 vs 53 ± 7 ng/ml; mean ± s.e.m.) on day 11. Serum prolactin levels at 0400 h on day 12 of pseudopregnancy were significantly (P<0·05) lower in the RU486-treated group than in the control group (16 ±4 vs 154 ±44 ng/ml; mean ± s.e.m.). The concomitant prolactin treatment reversed the luteolytic effects of RU486 on day 11 of pseudopregnancy. In hysterectomized PSP rats, RU486 also suppressed serum prolactin levels, and the concomitant prolactin treatment again reversed the luteolytic effects of RU486. In hysterectomized rats which were hypophysectomized and pituitary autotransplanted, RU486 treatment did not induce any significant changes in serum progesterone and prolactin levels. These results indicated that RU486 induced luteolysis during the late-luteal phase in PSP rats by suppressing prolactin secretion via a hypothalamic mechanism. Journal of Endocrinology (1996) 150, 93–98


1995 ◽  
Vol 133 (6) ◽  
pp. 701-717 ◽  
Author(s):  
Bernd Hinney ◽  
Christina Henze ◽  
Wolfgang Wuttke

Hinney B, Henze C, Wuttke W. Regulation of luteal function by luteinizing hormone and prolactin at different times of the luteal phase. Eur J Endocrinol 1995;133:701–17. ISSN 0804–4643 In 54 healthy women luteal function was assessed by sequential withdrawals of blood samples at 10-min intervals for 8–10 h. Subgroups of the women were studied during the early and late ovulatory period and during the early, mid- and late luteal phase. Bio- and immunoreactive luteinizing hormone (LH), prolactin, testosterone, estradiol and progesterone levels were determined in each sample. While the bio- and immunoreactivity of LH pulses correlated fairly well, a number of bio- or immunoreactive LH pulses were observed that were not detected by the respective other method. Responsivity of the corpus luteum to LH episodes developed during the second half of the luteal phase and was most marked in cases where LH episodes were accompanied by prolactin episodes. In the absence of prolactin episodes, LH episodes did not stimulate progesterone or estradiol secretion. The highest incidence of coincident LH and prolactin pulses was observed during the mid- and late luteal phase. Serum testosterone levels showed also some fluctuations but these were independent of immuno- or bioactive LH episodes and therefore most likely not of luteal origin. Prior to menstruation LH episodes were not any more stimulatory to progesterone secretion, indicating that it is not the withdrawal of LH but, rather, another possibly intraovarian mechanism that results in luteolysis. In a number of women, increased estradiol and progesterone secretion was strictly related to the prior occurrence of LH and prolactin pulses. In other subjects, both gonadal steroids fluctuated largely with no discernible correlation to LH fluctuations. This may indicate that in these subjects the corpora lutea have some degree of autonomous regulation. W Wuttke, Abteilung für Klinische und Experimentelle Endokrinologie, Universitäts-Frauenklinik, Robert-Koch-Strasse 40, D-37075 Gottingen, Germany


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