Inhibition of progesterone secretion by a 3β-hydroxysteroid dehydrogenase inhibitor in late pregnant sheep

1985 ◽  
Vol 63 (2) ◽  
pp. 136-142 ◽  
Author(s):  
Graham Jenkin ◽  
Geoffrey D. Thorburn
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Placental Lactogen ◽  
Plasma Progesterone ◽  
Progesterone Secretion ◽  
Pregnant Sheep ◽  
Plasma Estradiol ◽  
Prostaglandin F ◽  
Essential Prerequisite ◽  
Estradiol 17Β

The role of progesterone in the initiation of parturition in the sheep is unclear. Whether a decrease in plasma progesterone is the essential prerequisite for the initiation of parturition or whether other factors also maintain uterine quiescence until delivery is not known. The effect of withdrawal of progesterone on the initiation of parturition has been investigated by intravenous administration of trilostane, a 3β-hydroxysteroid dehydrogenase Δ5−4 isomerase inhibitor, to late pregnant sheep. Twenty-five or 100 mg trilostane caused a precipitous decrease in plasma progesterone to about 30% of preinjection levels. Progesterone remained depressed for up to 7 days after treatment. 13,14-Dihydro-15-keto-prostaglandin F2α (PGFM) became elevated between 7 and 36 h after trilostane injection but gradually returned to preinjection levels during the subsequent 36 h, at a time when plasma progesterone was still depressed. Four of 11 animals treated with 100 or 200 mg trilostane aborted prematurely at a time when plasma PGFM was maximal and plasma progesterone minimal. There were no consistent changes in plasma estradiol-17β or ovine placental lactogen concentrations after treatment with trilostane. It is suggested that a decrease in plasma progesterone will cause a transient increase in plasma PGFM concentrations which can lead to the premature initiation of parturition. In some instances the myometrium does not appear to respond to the elevated PGFM concentrations even when the estrogen:progesterone ratio is elevated by a decrease in plasma progesterone.

Attenuation of preovulatory gonadotrophin surges by epostane: a new inhibitor of 3β-hydroxysteroid dehydrogenase

1988 ◽  
Vol 118 (1) ◽  
pp. 59-68 ◽  
Author(s):  
L. V. DePaolo
Keyword(s):  
Peak Plasma ◽  
Plasma Concentrations ◽  
Hydroxysteroid Dehydrogenase ◽  
Inhibitory Effects ◽  
Plasma Progesterone ◽  
Ru 486 ◽  
Progesterone Secretion ◽  
Progesterone Antagonist

ABSTRACT Epostane, an inhibitor of 3β-hydroxysteroid dehydrogenase, was administered orally to pro-oestrous rats to evaluate further a possible role for preovulatory progesterone secretion in eliciting surges of LH and FSH. Whereas a dose of 10 mg epostane/kg had essentially no effects on preovulatory gonadotrophin surges and ovulation, 200 mg epostane/kg markedly attenuated LH and FSH surges and blocked ovulation. A dose of 50 mg epostane/kg exerted effects on LH and FSH surges and ovulation intermediate between those of doses of 10 and 200 mg/kg. Plasma concentrations of progesterone were significantly lower in all anovulatory epostane-treated rats at 18.00 and 22.00 h on pro-oestrus than those measured in vehicle-treated rats. Concurrent injection of 2 mg progesterone in rats given 200 mg epostane/kg restored gonadotrophin surges to normal, but consistently failed to reverse the inhibitory effects of epostane on ovulation. Peak plasma progesterone levels produced by the progesterone injections were eight- to tenfold higher than the highest levels measured in vehicle-treated rats during the afternoon of pro-oestrus. Insertion of progesterone capsules was less effective than injections of progesterone in restoring gonadotrophin surges to normal, even though peak plasma progesterone concentrations achieved after insertion of two 20 mm long progesterone capsules were double the peak progesterone concentrations measured in control rats. Nevertheless, taken together with recent reports showing attenuation of preovulatory gonadotrophin surges by the progesterone antagonist RU 486 (17β-hydroxy-11β-[4-dimethyl-aminophenyl]-17α-[prop-1-ynl]estra-4,9-diene-3-one), the present results provide support for a role of preovulatory progesterone secretion in enhancing oestrogen-dependent LH/FSH surges on pro-oestrus. J. Endocr. (1988) 118, 59–68

Regulation of ovine placental lactogen: lack of correlation with progesterone secretion

1982 ◽  
Vol 95 (2) ◽  
pp. 275-279 ◽  
Author(s):  
M. J. Taylor ◽  
G. Jenkin ◽  
J. S. Robinson ◽  
G. D. Thorburn
Keyword(s):  
Dehydrogenase Activity ◽  
Hydroxysteroid Dehydrogenase ◽  
Placental Lactogen ◽  
Peripheral Plasma ◽  
Significant Fall ◽  
Progesterone Secretion ◽  
Pregnant Sheep ◽  
Significant Change

After administration of an inhibitor of 3β-hydroxysteroid dehydrogenase activity to late-pregnant sheep, a sharp and significant fall in progesterone concentrations in peripheral plasma was noted, and lowered levels were sustained for up to 24 h. However, no significant change in the secretion of ovine placental lactogen (oPL) was noted. These results indicate that progesterone secretion does not regulate secretion of oPL during pregnancy.

PLASMA PROGESTERONE LEVELS IN GUINEA-PIGS ACTIVELY IMMUNIZED AGAINST PROSTAGLANDIN F2α, HYSTERECTOMIZED OR TREATED WITH INTRA-UTERINE INDOMETHACIN

1975 ◽  
Vol 67 (1) ◽  
pp. 81-88 ◽  
Author(s):  
N. L. POYSER ◽  
E. W. HORTON
Keyword(s):  
Bovine Serum Albumin ◽  
Serum Albumin ◽  
Guinea Pigs ◽  
Bovine Serum ◽  
Prostaglandin F2α ◽  
Corpora Lutea ◽  
Plasma Progesterone ◽  
Progesterone Secretion ◽  
Bovine Serum Albumin Conjugate ◽  
Prostaglandin F

SUMMARY Five guinea-pigs actively immunized against a prostaglandin F2α(PGF2α)–bovine serum albumin conjugate showed elongated oestrous cycles. During these, corpora lutea were maintained in a functional secretory state as indicated by plasma progesterone levels. The results are compatible with the view that the PGF2α antibodies neutralized the PGF2α released from the uterus and thus prevented its normal luteolytic effect. Similar patterns of progesterone secretion were observed in two hysterectomized animals and in two animals with intra-uterine implants of indomethacin.

EFFECT OF PROGESTERONE WITHDRAWAL IN SHEEP DURING LATE PREGNANCY

1982 ◽  
Vol 92 (1) ◽  
pp. 85-93 ◽  
Author(s):  
M. J. TAYLOR ◽  
R. WEBB ◽  
M. D. MITCHELL ◽  
J. S. ROBINSON
Keyword(s):  
Dehydrogenase Activity ◽  
Plasma Concentrations ◽  
Late Pregnancy ◽  
Hydroxysteroid Dehydrogenase ◽  
Peripheral Plasma ◽  
Activity Concentrations ◽  
Pregnant Sheep ◽  
Prostaglandin F

The concentration of progesterone in the peripheral plasma of seven sheep during late pregnancy was reduced by injection of an inhibitor of 3β-hydroxysteroid dehydrogenase activity. Concentrations of progesterone were 10·0± 1·0(s.e.m.) ng/ml (n = 6) before injection of the inhibitor, fell to 1·39 ± 0·40 ng/ml (n = 6) 30 min after injection, and remained within this lowered range for 6 h after injection. By 20–24 h and 30–35 h after injection progesterone concentrations had recovered to 4·63±0·94 and 14·07 ±4·17 ng/ml respectively (n = 6). Six out of seven ewes delivered prematurely 32·5± 2·9 h after injection. Delivery appeared to be normal, and was associated with increasing concentrations of 13,14-dihydro-15-oxo prostaglandin F2α in peripheral plasma. Concentrations of oestradiol-17β17β in peripheral plasma were slightly raised immediately before delivery, at which time progesterone concentrations were within the preinjection range. These data suggest that progesterone withdrawal is one mechanism that initiates increased prostaglandin F2α secretion in the pregnant sheep.

Induction of transient functional luteolysis in cyclic sheep by a 3 β-hydroxysteroid dehydrogenase inhibitor

1984 ◽  
Vol 100 (1) ◽  
pp. 61-66 ◽  
Author(s):  
G. Jenkin ◽  
R. T. Gemmell ◽  
G. D. Thorburn
Keyword(s):  
Luteal Phase ◽  
Competitive Inhibition ◽  
Ovarian Tissue ◽  
Hydroxysteroid Dehydrogenase ◽  
Oestrous Cycle ◽  
Morphological Examination ◽  
Plasma Progesterone ◽  
Luteal Regression ◽  
Luteal Function ◽  
Prostaglandin F

ABSTRACT The mechanism by which prostaglandin F2α terminates luteal function in the sheep is unclear even though it is used extensively in animal husbandry. At the time of luteal regression, a decrease in 3β-hydroxysteroid dehydrogenase (3β-HSD) activity is apparent in the corpus luteum, but it is not known whether the decrease in enzyme activity is the primary cause of structural luteolysis. The effect of trilostane, a 3β-HSD inhibitor, on luteal function and morphology has therefore been investigated. Intravenous injection of trilostane in the mid-luteal phase of the oestrous cycle caused a decrease in ovarian tissue progesterone content. A transient decrease in peripheral and utero-ovarian vein plasma progesterone was observed but there was no significant effect on the length of the luteal phase of the cycle. There was no significant change in plasma 13,14-dihydro-15-oxo-prostaglandin F2α during the period when plasma progesterone was depressed. Morphological examination of the corpora lutea revealed a decrease in the concentration of electron-dense granules without any other features of impending luteal regression. When plasma progesterone was reduced for more than 10 h by two injections of trilostane 4 h apart, there was again no subsequent effect on the length of the oestrous cycle or on the return to oestrus. Plasma progesterone returned to preinjection levels within 24 h of injection. This evidence suggests that competitive inhibition of 3β-HSD activity, per se, is ineffective in bringing about structural luteolysis. J. Endocr. (1984) 100, 61–66

scholarly journals Studies on the role of zinc in parturition in the rat

1983 ◽  
Vol 210 (3) ◽  
pp. 761-767 ◽  
Author(s):  
G E Bunce ◽  
G R Wilson ◽  
C F Mills ◽  
A Klopper
Keyword(s):  
Dehydrogenase Activity ◽  
Hydroxysteroid Dehydrogenase ◽  
Zn Deficiency ◽  
Progesterone Concentration ◽  
Pregnant Rats ◽  
Plasma Progesterone ◽  
Prostaglandin F2 Alpha

1. Pregnant rats were fed either low (less than 1 p.p.m.) Zn or control (40 p.p.m. Zn) diets from day 10 of gestation. They were killed at intervals during the last 96 h preceding the normal time for onset of parturition, and differences in plasma progesterone, oestradiol-17 beta and ovarian 20 alpha-hydroxysteroid dehydrogenase were assessed. 2. Gestation was prolonged in Zn-deficient rats. 3. Although the preparturient decline in plasma progesterone began at the same time in all groups, at term, plasma progesterone concentration in Zn-deficient rats remained significantly higher than in normal females. 4. Induction of ovarian 20 alpha-hydroxysteroid dehydrogenase activity was delayed by about 8 h by Zn deficiency. This delay was not observed if prostaglandin F2 alpha was injected previously. 5. The results suggest a Zn-dependent step(s) in uterine synthesis and/or release of prostanoids.

USE OF MECLOFENAMIC ACID TO INVESTIGATE THE ROLE OF PROSTAGLANDIN BIOSYNTHESIS DURING INDUCED PARTURITION IN SHEEP

1978 ◽  
Vol 76 (1) ◽  
pp. 101-109 ◽  
Author(s):  
M. D. MITCHELL ◽  
A. P. F. FLINT
Keyword(s):  
Maternal Plasma ◽  
Cervical Ripening ◽  
Uterine Contractility ◽  
Expected Time ◽  
Uterine Contractions ◽  
Meclofenamic Acid ◽  
Pregnant Sheep ◽  
Prostaglandin F ◽  
Maternal Administration

SUMMARY The maternal administration of meclofenamic acid (a prostaglandin synthetase inhibitor) to pregnant sheep prevented the dexamethasone-induced delivery of live lambs and delayed delivery after foetal death in utero. Administration of meclofenamic acid had no effect on the changes in the levels of progesterone and oestrogen in the plasma which occur before lambing in response to foetal glucocorticoid. Despite normal maternal endocrine changes, increased uterine activity did not occur at the expected time, although it could be elicited by vaginal distension or by administration of oxytocin. The rates of cervical ripening and dilatation were reduced by meclofenamic acid and lambing was frequently associated with some degree of cervical dystocia. Withdrawal of meclofenamic acid did not immediately result in an increase in the level of prostaglandin F in the plasma despite the appearance of co-ordinated uterine contractions; the concentration of prostaglandin in the plasma was not raised until vaginal passage of the lambs. It is concluded that the synthesis or release of prostaglandins mediates the effects of changes in the levels of steroids in the maternal plasma on uterine contractility in sheep.

Plasma estradiol-17β, progesterone, prostaglandin F, and prostaglandin E2 concentrations during natural oviposition in the loggerhead turtle (Caretta caretta)

1991 ◽  
Vol 82 (1) ◽  
pp. 121-130 ◽  
Author(s):  
Louis J. Guillette ◽  
Karen A. Bjorndal ◽  
Alan B. Bolten ◽  
Timothy S. Gross ◽  
Brent D. Palmer ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Loggerhead Turtle ◽  
Caretta Caretta ◽  
Plasma Estradiol ◽  
Prostaglandin F ◽  
Estradiol 17Β

scholarly journals Mechanism of action of noradrenaline on secretion of progesterone and oxytocin by the bovine corpus luteum in vitro

2001 ◽  
Vol 49 (1) ◽  
pp. 39-51 ◽  
Author(s):  
Grażyna Miszkiel ◽  
J. Kotwica
Keyword(s):  
Corpus Luteum ◽  
Mechanism Of Action ◽  
Hydroxysteroid Dehydrogenase ◽  
Luteal Cells ◽  
Progesterone Secretion ◽  
Bovine Corpus Luteum ◽  
Progesterone Synthesis ◽  
Luteal Tissue ◽  
Prostaglandin F

The present studies were conducted: (1) to determine which β-adrenoceptor subtypes are involved in progesterone and oxytocin (OT) secretion, (2) to examine whether noradrenaline (NA) acts directly on the cytochrome P-450scc and 3β-hydroxysteroid dehydrogenase (3β-HSD), and (3) to study the effect of prostaglandin F2α, (PGF2α) on NA-stimulated steroidogenesis in luteal cells. The effect of NA on progesterone secretion from luteal slices of heifers on days 8–12 of the oestrous cycle was blocked by both atenolol (β1-antagonist) and ICI 118.551 hydrochloride (β2-antagonist). OT secretion was blocked only after treatment with ICI 118.551 hydrochloride (P < 0.05). Dobutamine (10−4−10−6), a selective β1 agonist and salbutamol (10−4−10−6), a selective β2 agonist, both increased progesterone production (P < 0.01) with an efficiency comparable to that produced by NA (P < 0.01). The increase of OT content in luteal slices was observed only after treatment with salbutamol at the dose of 10−5M (P < 0.01). Dobutamine had no effect on OT production at any dose. A stimulatory effect of NA on cytochrome P-450scc activity (P < 0.05) was demonstrated using 25-hydroxycholesterol as substrate. 3β-HSD activity also increased following NA (P < 0.01) or pregnenolone (P < 0.05) and in tissue treated with pregnenolone together with NA (P < 0.01). PGF decreased progesterone synthesis (P < 0.05) and 3β-HSD activity (P < 0.01) in tissue treated with NA. We conclude that NA stimulates progesterone secretion by luteal β1- and β2-adrenoceptors, while OT secretion is probably mediated only via the β2-receptor. NA also increases cytochrome P-450scc and 3β-HSD activity. PGF inhibits the luteotropic effect of NA on the luteal tissue.

The acute effect of placentectomy and hysterectomy on peripheral plasma progesterone levels and ovarian progesterone secretion in the pregnant rat

1983 ◽  
Vol 98 (1) ◽  
pp. 71-77 ◽  
Author(s):  
J. K. Olynyk ◽  
N. W. Bruce ◽  
B. J. Waddell
Keyword(s):  
Acute Effect ◽  
Initial Experiment ◽  
Direct Role ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Plasma Progesterone ◽  
Peripheral Plasma ◽  
Progesterone Secretion ◽  
And Control

The role of placental luteotrophins in modulating plasma progesterone concentrations and ovarian progesterone secretion was examined in 16-day pregnant rats. In an initial experiment rats were placentectomized and their plasma progesterone concentrations monitored for 24 h; the rats were conscious within 30 min of placentectomy. Relative to control values, progesterone concentrations fell significantly within 0·5 h. A venous outflow technique was then used to monitor rates of progesterone secretion from ovaries of hysterectomized and control rats maintained under anaesthesia. Hysterectomy had no apparent effect on either progesterone secretion or plasma progesterone concentrations for at least 2 h. A final experiment was carried out to compare the effects of hysterectomy on plasma progesterone concentrations in conscious rats with those of placentectomized rats of the first experiment. Progesterone concentrations did not change significantly in hysterectomized rats for 4 h but fell to very low values by 24 h. These results suggest that placental luteotrophins do not have an acute, direct role in the control of plasma progesterone levels but are needed to maintain progesterone secretion in the longer term and possibly inhibit uterine luteolysin release.

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