Effect of difluoromethylornithine on the LH surge and subsequent ovulation in the rat

1988 ◽  
Vol 117 (3) ◽  
pp. 447-453 ◽  
Author(s):  
S. A. Nicholson ◽  
M. Aslam ◽  
T. T. Chuang ◽  
B. Gillham ◽  
M. T. Jones
Keyword(s):  
Ornithine Decarboxylase ◽  
Plasma Concentrations ◽  
Specific Inhibitor ◽  
Steroid Production ◽  
Lh Surge ◽  
Direct Observations ◽  
Steroid Dependent ◽  
Lh Release ◽  
Plasma Oestradiol

ABSTRACT Female Wistar-derived rats with regular oestrous cycles were injected s.c. at 15.00 h on pro-oestrus with difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase. The drug (10–100 mg/rat) caused a dose-related reduction in the concentration of LH in plasma taken at 19.00 h (the time of the peak of the LH surge in this colony). There was also a dose-related reduction in the pituitary content of total polyamines. The reduction in the plasma concentration of LH was not due to the shifting of the time of the peak of the surge, as concentrations were significantly lower than control from 17.00 to 21.00 h, the overall reduction in total LH release being approximately 50%. The number of ova in the oviducts at 06.00 h next morning was significantly reduced by treatment with 50 mg DFMO/rat, by an average of 70%. Injection of DFMO enhanced the fall in plasma oestradiol concentrations seen between 15.00 and 19.00 h, in a dose-related manner. It also prevented the rise in progesterone concentrations seen in control animals during this period. The ability of DFMO to prevent the rise in plasma concentrations of LH was not secondary to the effects of the drug on ovarian steroid production because DFMO also significantly reduced the LH surge in animals ovariectomized on dioestrus and given appropriate replacement injections of oestradiol and progesterone. It seems possible that part of the action of DFMO is exercised at the hypothalamus, since when 50 mg DFMO/rat was given either 2 or 4 h before the expected peak of the LH surge, the LHRH content of the hypothalamus was significantly reduced at that time. These results suggest that activation of ornithine decarboxylase is a necessary prerequisite for a normal LH surge, and that this activation is steroid-dependent. This conclusion is borne out by results from direct observations on the activity of the enzyme in pituitary tissue incubated in vitro. J. Endocr. (1988) 117, 447–453

Oxytocin has a role in gonadotrophin regulation in rats

1990 ◽  
Vol 125 (3) ◽  
pp. 425-432 ◽  
Author(s):  
G. Robinson ◽  
J. J. Evans
Keyword(s):  
Follicular Development ◽  
Pituitary Cells ◽  
Lh Surge ◽  
Rat Pituitary ◽  
Lh Release ◽  
Rat Pituitary Cells ◽  
Dose Dependent ◽  
In Vivo Administration

ABSTRACT We previously demonstrated that oxytocin stimulates LH release from rat pituitary cells in vitro and advances follicular development and ovulation in mice in vivo. This study reports an investigation of rat LH levels following in-vivo administration of oxytocin. Injection of oxytocin (10 mIU/g, i.p.) to rats at 07.00, 08.00 and 09.00 h of pro-oestrus or at 09.00, 10.00 and 11.00 h of pro-oestrus advanced the onset of the LH surge (P<0.005) and attainment of peak concentrations of LH (P<0.02) in peripheral blood. On the other hand, the descending phase of the LH surge and the surge amplitude were not altered by oxytocin. Treatment at 05.00, 06.00 and 07.00 h of pro-oestrus or at 11.00, 12.00 and 13.00 h of pro-oestrus had no effect on the LH profile. A higher oxytocin dose (20 mIU/g) inhibited LH release when treatment was begun at 05.00, 07.00 or 09.00 h of pro-oestrus. A lower dose (5 mIU/g) was ineffective in altering LH concentrations. In addition, injections of oxytocin (10 mIU/g) at oestrus, metoestrus or dioestrus had no effect on the release of LH. Thus the efficacy of oxytocin in altering concentrations of LH was dose dependent and also critically affected by the day of the oestrous cycle and the time of pro-oestrus. Removal of endogenous oxytocin activity by the use of an oxytocin receptor antagonist abolished the pro-oestrous LH surge, indicating that oxytocin is a vital physiological component of the LH-releasing mechanism in rats. The study provides unequivocal evidence that oxytocin induces LH release in vivo, but the manifestation of oxytocin activity is dependent upon conditions of exposure. Journal of Endocrinology (1990) 125, 425–432

Parachlorophenylalanine blocks the spontaneous pro-oestrous surge of prolactin as well as LH and affects the secretion of oestradiol-17β

1985 ◽  
Vol 104 (3) ◽  
pp. 415-418 ◽  
Author(s):  
A. M. Horn ◽  
G. Fink
Keyword(s):  
Plasma Concentrations ◽  
Female Rats ◽  
Central Action ◽  
Lower Plasma ◽  
Synthesis Inhibitor ◽  
Lh Surge ◽  
Peripheral Effect ◽  
Plasma Oestradiol

ABSTRACT The effect of the 5-hydroxytryptamine synthesis inhibitor, parachlorophenylalanine (PCPA), on the spontaneous, pro-oestrous surges of prolactin and LH was investigated in conscious female rats implanted with an intra-atrial cannula. The LH surge was blocked in all animals treated with PCPA, but the prolactin surge was blocked in six out of ten animals and unaffected in four out of ten animals. There was a significant correlation between the plasma concentrations of prolactin and oestradiol-17β, surges of prolactin occurred in animals with plasma oestradiol-17β concentrations of 120 pmol/l and above, and the LH surge was blocked in animals in which the oestradiol-17β concentration was less than 188 pmol/l plasma. These results show that (i) PCPA can block the pro-oestrous prolactin as well as the LH surge, (ii) in addition to a central action PCPA may depend also on its peripheral effect on the secretion of oestradiol-17β and (iii) on average, lower plasma concentrations of oestradiol-17β are required for triggering the prolactin compared with the LH surge. J. Endocr. (1985) 104, 415–418

Changes in plasma LRH during the normal menstrual cycle in women

1980 ◽  
Vol 93 (3) ◽  
pp. 257-263 ◽  
Author(s):  
A. Miyake ◽  
Y. Kawamura ◽  
T. Aono ◽  
K. Kurachi
Keyword(s):  
Menstrual Cycle ◽  
Luteal Phase ◽  
Plasma Concentrations ◽  
Mean Value ◽  
Lh Surge ◽  
Double Antibody ◽  
Normal Menstrual Cycle ◽  
The Mean ◽  
Plasma Oestradiol

Abstract. The plasma concentrations of immunoreactive LRH, LH, FSH, oestradiol and progesterone were measured daily by a sensitive double antibody radioimmunoassay during 12 cycles of 8 normal cyclic women. The mean (± se) immunoreactive LRH levels in the follicular and luteal phase except the immunoreactive LRH peaks during normal cycles were 4.18 ± 0.38 pg/ml and 4.50 ± 0.45 pg/ml, respectively. The immunoreactive LRH peaks were observed in 11 of 12 cycles, appearing on day −4 to −1 from the LH surge in 9 cycles and on day +1 and +2 in 2 cycles. The mean value of immunoreactice LRH peaks was 42.0 ± 11.4 pg/ml with range of 12 to 154 pg/ml. The immunoreactive LRH peak lasted for one day in 10 cycles and for 4 days in one cycle. The immunoreactive LRH peaks in different cycles of the same women did not occur on the same day relative to the LH peak. The plasma immunoreactive LRH levels measured every 10 min for 40 min periods every day in normal cyclic women during the ovulatory phase showed slight, but not significant fluctuations. Plasma oestradiol levels began to increase on day −6, reaching a peak on day − 1, and were followed by peaks of LH and FSH. These data indicate that increase in serum oestradiol was followed by release of LRH from the hypothalamus and pre-ovulatory discharge of gonadotrophins from the pituitary.

scholarly journals In vitro effect of leptin on LH release by anterior pituitary glands from female rats at the time of spontaneous and steroid-induced LH surge

2001 ◽  
pp. 659-665 ◽  
Author(s):  
SN De Biasi ◽  
LI Apfelbaum ◽  
ME Apfelbaum
Keyword(s):  
Estrous Cycle ◽  
Anterior Pituitary ◽  
Female Rats ◽  
Female Rat ◽  
Lh Surge ◽  
Pituitary Glands ◽  
Lh Release ◽  
Vitro Effect ◽  
Stimulation Of

OBJECTIVE: The purpose of this work was to study the direct effect of leptin on LH release by anterior pituitary glands from female rats at the time of spontaneous and steroid-induced LH surge. METHODS: LH responsiveness to leptin by pituitaries from rats killed in the afternoon (1500 h) at different stages of the 4-day estrous cycle (diestrus-1: D1; diestrus-2: D2; proestrus; estrus), ovariectomized (OVX; 15 days post-castration) and ovariectomized steroid-primed (OVX-E(2)/Pg; pretreated with 5 microg estradiol and 1 mg progesterone), was evaluated in vitro. Hemi-adenohypophyses were incubated in the presence of synthetic murine leptin for 3 h. RESULTS: Addition of increasing concentrations of leptin (0.1-100 nmol/l) to the incubation medium of proestrus pituitaries produced a dose-related stimulation of LH release; the maximal increase to 315% of control was obtained with 10 nmol/l leptin. Leptin (10 nmol/l) enhanced LH release at all days of the estrous cycle, the greatest response occurring in proestrus (318%) and the lowest at D1 (123%). In order to evaluate the role of nitric oxide (NO) in the action of leptin on LH release, glands from proestrus rats were incubated in the presence of 10 nmol/l leptin with or without 0.3 mmol/l N(G)-monomethyl-l-arginine (NMMA), a competitive inhibitor of NO synthase (NOS). NMMA completely suppressed the stimulation of LH release induced by leptin. Leptin also stimulated LH release by pituitaries from OVX rats, and treatment with steroid hormones led to a marked increase in the response (OVX: 162% compared with OVX-E(2)/Pg: 263%; P<0.05). For comparative analysis, a similar experimental procedure was carried out using GnRH (10 nmol/l). Leptin acts at the pituitary level in a similar manner as GnRH, although with significantly lower potency. CONCLUSIONS: These results confirm and extend previous reports regarding a direct action of leptin at the pituitary level, stimulating LH release by anterior pituitaries from female rats at the time of spontaneous and steroid-induced LH surge. In the female rat pituitary this leptin action is controlled by gonadal steroids and mediated by NO.

In-vivo inhibition of the preovulatory LH surge by substance P and in-vitro modulation of gonadotrophin-releasing hormone-induced LH release by substance P, oestradiol and progesterone in the female rat

1991 ◽  
Vol 130 (2) ◽  
pp. 169-175 ◽  
Author(s):  
T. Battmann ◽  
S. Mélik Parsadaniantz ◽  
B. Jeanjean ◽  
B. Kerdelhué
Keyword(s):  
Substance P ◽  
Inhibitory Effect ◽  
Female Rat ◽  
Neuroendocrine Control ◽  
Lh Surge ◽  
Releasing Hormone ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone

ABSTRACT The effects of substance P (SP) on the preovulatory surge of LH and on the inhibitory and stimulatory effects of oestradiol-17β and progesterone on gonadotrophin-releasing hormone (GnRH)-induced LH release were investigated in vivo and in vitro in the rat. A single s.c. injection of 100 μg SP at 12.00 h on the day of pro-oestrus significantly decreased the preovulatory surge of LH. In vitro, the inhibitory effect of oestradiol-17β on GnRH-induced LH release was not modified by treatment with SP. The stimulatory effect of progesterone on GnRH-induced LH release was reduced by treatment with SP. It is concluded that SP may play a modulatory role in the neuroendocrine control of the preovulatory LH surge. Journal of Endocrinology (1991) 130, 169–175

scholarly journals Kisspeptin Is Present in Ovine Hypophysial Portal Blood But Does Not Increase during the Preovulatory Luteinizing Hormone Surge: Evidence that Gonadotropes Are Not Direct Targets of Kisspeptin in Vivo

Endocrinology ◽  
2007 ◽  
Vol 149 (4) ◽  
pp. 1951-1959 ◽  
Author(s):  
J. T. Smith ◽  
A. Rao ◽  
A. Pereira ◽  
A. Caraty ◽  
R. P. Millar ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Culture Media ◽  
Pituitary Cell ◽  
Portal Blood ◽  
Lh Surge ◽  
Lh Release ◽  
Cell Fractions ◽  
Hypophysial Portal

There is strong evidence that kisspeptin acts to regulate GnRH secretion, but whether there is also a component of action on the gonadotropes is not clear. Using quantitative RT-PCR, we found that G protein-coupled receptor-54 mRNA is expressed in ovine pituitary cell fractions enriched for gonadotropes as well as in somatotropes and lactotropes. To test whether kisspeptin acts directly on the pituitary gonadotropes, we first examined LH release from primary ovine pituitary cell cultures treated with kisspeptin. We found that kisspeptin treatment increased the concentration of LH in culture media by 80%, compared with control, but only in pituitary cultures from ewes during the follicular phase of the estrous cycle. After this, we determined whether kisspeptin acts on the pituitary gland in vivo. Using GnRH-replaced ovariectomized hypothalamo-pituitary-disconnected ewes, we were not able to achieve any effect of kisspeptin on LH under steady-state conditions or during the period of an estrogen-induced LH surge. Finally, we collected hypophysial portal blood samples from ovariectomized ewes and measured kisspeptin levels. Low but detectable amounts of kisspeptin were found in portal plasma, but levels were similar in ovariectomized ewes that were untreated or given estrogen to elicit an LH surge. Thus, although we observed an effect of kisspeptin on LH release in vitro in some situations, similar findings were not obtained in vivo. Moreover, the low concentrations of kisspeptin in hypophysial portal blood and the lack of any change during the period of an estrogen-induced GnRH/LH surge suggest that action on the pituitary gland is not of major consequence in terms of LH release.

Role of tyrosine kinases in gastrin induction of ornithine decarboxylase in colonic mucosa

1990 ◽  
Vol 259 (4) ◽  
pp. G626-G630 ◽  
Author(s):  
A. P. Majumdar
Keyword(s):  
Ornithine Decarboxylase ◽  
Tyrosine Kinases ◽  
Colonic Mucosa ◽  
Specific Inhibitor ◽  
Irreversible Inhibitor ◽  
Mucosal Explants ◽  
Tyrosyl Phosphorylation ◽  
Stimulation Of

An organ culture system was utilized to evaluate the role of tyrosine kinases (Tyr-k) and tyrosine-specific phosphorylation of proteins in gastrin regulation of ornithine decarboxylase (ODC) activity in colonic mucosa. Exposure of colonic mucosal explants to gastrin (50-100 ng G-17 I/ml) resulted in a profound stimulation of both Tyr-k and ODC activities compared with the corresponding basal levels. Whereas the maximal stimulation (ranging between 70 and 150%) of Tyr-k occurred within 10-15 min of exposure to gastrin, ODC activity was significantly stimulated (180%) 2 h after exposure to the hormone, and at 4 h it was found to be 750% above the corresponding basal level. Difluoromethylornithine (DFMO; 2 mM), an irreversible inhibitor of ODC, completely abolished the gastrin-mediated stimulation of ODC but not Tyr-k activity. On the other hand, genistein (100 micrograms/ml), a specific inhibitor of Tyr-k, caused a total suppression of the gastrin-induced stimulation of both Tyr-k and ODC. Gastrin also stimulated tyrosyl phosphorylation of a colonic mucosal membrane protein with molecular mass of 57 kDa, and genistein greatly attenuated this effect. We conclude that gastrin stimulates colonic mucosal ODC in vitro, and Tyr-k may be required for the regulation of this process.

Analysis of the ratio of biological to immunological LH secreted during the oestrogen-induced LH surge in the ewe

1990 ◽  
Vol 127 (2) ◽  
pp. 217-222 ◽  
Author(s):  
I. J. Clarke ◽  
L. M. Foulds ◽  
S. Hayward ◽  
J. T. Cummins ◽  
D. M. Robertson
Keyword(s):  
Plasma Concentrations ◽  
Serum Samples ◽  
Lh Surge ◽  
Oestradiol Benzoate ◽  
Unknown Composition ◽  
Radio Immunoassay ◽  
Pass Through ◽  
Highly Correlated ◽  
The Relationship

ABSTRACT Plasma concentrations of in-vitro biological and immunological LH were measured throughout the LH surge in cyclic ewes and in ovariectomized ewes treated i.m. with oestradiol benzoate. Both activities increased in parallel during the LH surge in both groups, although the ratio of biological to immunological activities (B/I ratio) was highest at the peak of the LH surge. The two activities were highly correlated (r = 0·86–0·92), with similar slopes from their regression analysis for the cyclic and ovariectomized groups (1·15 and 1·16 respectively). However, the intercepts of the regression lines did not pass through the origin, but intersected the y (radio-immunoassay) axis, suggesting that these serum samples contained immunoactivity not associated with LH bioactivity. In conclusion, an increase in the LH B/I ratio was observed during the LH surge in oestrogen-treated ovariectomized ewes and in cyclic ewes. This increase was not attributable to a change in the relationship between these two LH activities during the LH surge, but rather to the detection of bioinactive immunoactive material in plasma of unknown composition. Journal of Endocrinology (1990) 127, 217–222

Blockade of pro-oestrus LH surge and ovulation by GABA increase in the rat locus coeruleus

1987 ◽  
Vol 115 (4) ◽  
pp. 490-496 ◽  
Author(s):  
Adriana I. Landa ◽  
Alfredo O. Donoso
Keyword(s):  
Locus Coeruleus ◽  
Plasma Concentrations ◽  
Aminobutyric Acid ◽  
Plasma Prolactin ◽  
Gamma Aminobutyric Acid ◽  
Gaba Transaminase ◽  
Lh Surge ◽  
Lh Release ◽  
Lh Secretion ◽  
Gaba Transaminase Inhibitor

Abstract. The effects of gamma-aminobutyric acid (GABA) increase at the nucleus locus coeruleus (LC) on pro-oestrus LH release and ovulation were evaluated in rats. Local microinjection of the GABA-transaminase inhibitor gamma-vinyl-GABA (GVG) produced 6 h later a marked increase in GABA in the LC. Such action caused a significant decrease of plasma LH levels and prevented the pro-oestrus LH surge. In some animals, plasma prolactin levels were also lowered, but in others its plasma concentrations were high and similar to that in controls. Ovulation did not occur in the rats treated with GVG. In additional experiments, the periventricular gray substance (PGS) close to the locus coeruleus was injected with GVG. Results obtained show a LH surge blockade and failure of ovulation in most of these rats. These findings may be interpreted on the basis of GABA action on rostral LC cells that project to the PGS. The results altogether suggest that through neurons of the locus coeruleus, GABA may exert an inhibitory role in the regulation of LH secretion.

Comparison of Specific Antibody, D-Phe-Pro-Arg-CH2Cl and Aprotinin for Prevention of In Vitro Effects of Recombinant Tissue-Type Plasminogen Activator on Haemostasis Parameters

1987 ◽  
Vol 58 (03) ◽  
pp. 921-926 ◽  
Author(s):  
E Seifried ◽  
P Tanswell
Keyword(s):  
Specific Antibody ◽  
Plasma Concentrations ◽  
Fibrinolytic Therapy ◽  
Tissue Type ◽  
Control Value ◽  
Type Plasminogen Activator ◽  
In Vitro Effects ◽  
Fibrinolytic Parameters

SummaryIn vitro, concentration-dependent effects of rt-PA on a range of coagulation and fibrinolytic assays in thawed plasma samples were investigated. In absence of a fibrinolytic inhibitor, 2 μg rt-PA/ml blood (3.4 μg/ml plasma) caused prolongation of clotting time assays and decreases of plasminogen (to 44% of the control value), fibrinogen (to 27%), α2-antiplasmin (to 5%), FV (to 67%), FVIII (to 41%) and FXIII (to 16%).Of three inhibitors tested, a specific polyclonal anti-rt-PA antibody prevented interferences in all fibrinolytic and most clotting assays. D-Phe-Pro-Arg-CH2Cl (PPACK) enabled correct assays of fibrinogen and fibrinolytic parameters but interfered with coagulometric assays dependent on endogenous thrombin generation. Aprotinin was suitable only for a restricted range of both assay types.Most in vitro effects were observed only with rt-PA plasma concentrations in excess of therapeutic values. Nevertheless it is concluded that for clinical application, collection of blood samples on either specific antibody or PPACK is essential for a correct assessment of in vivo effects of rt-PA on the haemostatic system in patients undergoing fibrinolytic therapy.

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