Differential effect of difluoromethylornithine on the increases in plasma concentrations of reproductive hormones on the afternoon of pro-oestrus in the rat

1989 ◽  
Vol 121 (3) ◽  
pp. 495-499 ◽  
Author(s):  
S. A. Nicholson ◽  
G. A. Wynne-Jones

ABSTRACT In our colony of female rats (220–320 g body weight) undergoing regular 4-day oestrous cycles there were significant, marked rises in concentrations of LH, FSH and prolactin between 09.00 and 19.00 h on pro-oestrus. The i.p. injection of difluoromethylornithine (DFMO; 40–400 mg/kg), a specific inhibitor of the activity of ornithine decarboxylase, at 15.00 h on prooestrus had a differential effect on the rise in plasma concentrations of the various hormones thereafter. The drug produced a significant, partial, dose-related suppression of the rise in plasma concentrations of LH and prolactin, but had no significant effect on the rise in FSH. For time-course studies, 120 mg DFMO/kg were injected at 13.00, 15.00 or 17.00 h and groups of animals killed at 19.00 h. Only the injection at 15.00 h was effective in causing a significant reduction in plasma concentrations of LH and prolactin at 19.00 h. Pituitary content of the hormones was found to be unaffected by the administration of DFMO at the times and doses tested. These results suggest that DFMO has a selective inhibitory effect on enhanced LH and prolactin secretion on the afternoon of pro-oestrus in the rat, whilst not affecting FSH release. There seems to be a limited time (after 13.00 but before 17.00 h) during which its administration is effective. Journal of Endocrinology (1989) 121, 495–499

1978 ◽  
Vol 79 (2) ◽  
pp. 239-240 ◽  
Author(s):  
A. BARTKE ◽  
M. MASON ◽  
S. DALTERIO ◽  
F. BEX

Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts 01545, U.S.A. (Received 2% March 1978) Tamoxifen (trans 1-(p-β-dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene; ICI 46,474) is both a potent antioestrogen and a weak oestrogen (Harper & Walpole, 1967) and is thought to act by inhibiting the binding of oestradiol to its cytoplasmic receptor (Jordan & Koerner, 1975). Chronic treatment with tamoxifen causes atrophy of the male accessory reproductive glands and the testicular germinal epithelium in the rat (Harper & Walpole, 1967) and the dog (M. Mason, unpublished data), as well as depression of the plasma concentration of testosterone in the latter species (M. Mason & A. Bartke, unpublished data). A direct inhibitory effect of tamoxifen on testicular steroidogenesis was suspected because treatment of female rats with tamoxifen increases, rather than decreases, the plasma concentration of luteinizing hormone (LH; Watson, Anderson, Alam, O'Grady & Heald, 1975). The possibility that an antioestrogen might act directly is of interest since


1995 ◽  
Vol 145 (3) ◽  
pp. 449-454 ◽  
Author(s):  
J Th J Uilenbroek ◽  
P van der Schoot ◽  
J A M Mattheij ◽  
J J M Swarts

Abstract To study the effects of the antiprogestagen RU486 on luteal activity in pseudopregnant rats, adult female rats made pseudopregnant by sterile copulation were given daily injections with oil vehicle or with RU486 (2 mg/day) either during the entire period of pseudopregnancy (day 1 till day 14) or during the second half of pseudopregnancy (day 8 till day 14). Blood was taken every other day to measure serum concentrations of progesterone. At autopsy, on day 15, the weights of ovaries, isolated corpora lutea and pituitary glands were recorded. In a second study using the same experimental protocol, blood was taken via a jugular vein cannula on days 8, 9, 10 and 11 after induction of pseudopregnancy; on each of these days blood samples were taken at 0700, 0800 and 0900 h, and at 1700, 1800 and 1900 h to measure plasma concentrations of prolactin, LH and progesterone. Administration of RU486 from day 1 of pseudopregnancy onwards had no effect on the increasing concentrations of serum progesterone during the first half of pseudopregnancy. Thereafter progesterone concentrations increased further in RU486-treated rats whereas they decreased in oil-treated pseudopregnant rats. Administration of RU486 from day 8 of pseudopregnancy onwards resulted in a decline in progesterone concentrations in serum on day 10 followed by ovulation on day 11. Plasma LH concentrations in rats treated with RU486 from day 1 of pseudopregnancy were higher than those in oil-treated rats on days 8, 9, 10 and 11. Treatment from day 8 of pseudopregnancy resulted in low LH concentrations at days 8 and 9 and the presence of a preovulatory surge of LH on the afternoon of day 10 (day of pro-oestrus). Plasma concentrations of prolactin measured in oil-treated rats showed two daily surges of similar magnitude in the morning and afternoon of days 8, 9, 10 and 11. In animals treated with RU486 from day 8 onwards, the afternoon surge on day 9 and the morning surge on day 10 were absent. This demonstrated that the luteolytic effect of RU486 when given during the second part of pseudopregnancy is due to a blockade in the afternoon surge of prolactin on day 9. In animals treated with RU486 from day 1 of pseudopregnancy onwards, prolactin in the early morning samples was low, while prolactin in the afternoon samples was highly elevated. At autopsy on day 15, the weights of ovaries, corpora lutea and pituitary glands in animals treated with RU486 from day 1 were larger than those in oil-treated rats; this is in line with an increased secretion of prolactin. In contrast, in animals treated with RU486 from day 8, pituitary weight was not elevated and the increase in ovarian weight was due to the presence of two generations of corpora lutea. In conclusion, whether or not RU486 is luteolytic in pseudopregnant rats depends on the time of administration: injection during the second half of pseudopregnancy inhibits prolactin secretion and induces luteolysis, while administration during the early phase of pseudopregnancy results in high concentrations of prolactin in the early afternoon and therefore prevents luteolysis. Journal of Endocrinology (1995) 145, 449–454


1996 ◽  
Vol 135 (4) ◽  
pp. 464-468 ◽  
Author(s):  
Leonor Pinilla ◽  
Dolores González ◽  
Manuel Tena-Sempere ◽  
Rafaela Aguilar ◽  
Enrique Aguilar

Pinilla L, González D, Tena-Sempere M, Aguilar R, Aguilar E. Effects of N-methyl-d-aspartate and kainic acid on prolactin secretion in prepubertal female rats. Eur J Endocrinol 1996;135:464–8. ISSN 0804–4643 The control of prolactin (PRL) secretion by N-methyl-d-aspartate (NMDA) and kainic acid (KA), agonists of NMDA and kainate receptors, and the interactions between NMDA and KA with nitric oxide (NO) were analysed in prepubertal female rats. For this purpose, serum PRL concentrations and hypothalamic and pituitary dopamine (DA) and serotonin (5-HT) concentrations were measured in females injected with NMDA, KA or two blockers of NO synthase: Nw-nitro-l-arginine methyl ester (NAME) and Nw-nitro-l-arginine (NA). Also, the effects of combined administration of NMDA and KA with the blockers of NO synthase were analyzed. We found that PRL release was inhibited 15 min after NMDA and KA administration, an effect probably mediated through the release of hypothalamic DA, as shown by the higher pituitary DA concentrations after NMDA or KA administration. The inhibitory effect of NMDA was preceded by an increase in serum PRL levels, observed at 5 and 10 min after NMDA administration. Nw-Nitro-l-arginine methyl ester alone inhibited prolactin secretion, and both NAME and NA abolished the inhibitory effect of KA, but not that of NMDA. We conclude that administration of NMDA exerted a dual action on PRL secretion: initially DA release was inhibited, leading to an increase in PRL secretion that in turn stimulated DA release and decreased serum PRL concentrations. Kainic acid also inhibited PRL secretion by releasing DA, an effect blocked by NO synthase inhibitors. Enrique Aguilar, Department of Physiology, Faculty of Medicine, University of Córdoba, E-14004, Spain


1989 ◽  
Vol 120 (2) ◽  
pp. 269-273 ◽  
Author(s):  
A. López-Calderón ◽  
C. Ariznavarreta ◽  
M. D. Calderón ◽  
J. A. F. Tresguerres ◽  
M. I. Gonzalez-Quijano

ABSTRACT The response of prolactin to chronic stress in intact, adrenalectomized and adrenomedullectomized male rats was studied. Immobilization stress in intact animals induced a significant increase in plasma concentrations of prolactin after 20 and 45 min and a significant decrease when the rats were submitted to chronic restraint (6 h daily for 4 days). Five weeks after adrenomedullectomy, plasma prolactin and corticosterone responses to chronic stress were not modified. In contrast, the inhibitory effect of chronic stress on prolactin secretion was totally suppressed by adrenalectomy. When treated with dexamethasone during the 4 days of restraint, adrenalectomized stressed rats showed similar plasma concentrations of prolactin to the intact stressed rats. These data indicate that the adrenal cortex is able to play an inhibitory role on prolactin secretion during stress only through a prolonged release of glucocorticoids. Journal of Endocrinology (1989) 120, 269–273


1986 ◽  
Vol 109 (3) ◽  
pp. 313-320 ◽  
Author(s):  
A. M. Bentley ◽  
M. Wallis

ABSTRACT Experiments were carried out on the antagonistic effects of opiates on the inhibition by dopamine of prolactin secretion from rat anterior pituitary glands. Dose–response and time-course experiments were carried out using both static incubation of paired hemipituitary glands and perifusion of whole glands. Dopamine (10–1000 nmol/l) was found to have an inhibitory effect on prolactin secretion, but at a lower concentration (0·1 nmol/l) a small stimulation was observed. Against an inhibition established with 100 nmol dopamine/l in static incubation, the three opiates under study, morphine sulphate, Leu5enkephalin and d-Ala2,Met5-enkephalin (DAME), had a maximum antagonistic effect at 50–1000 nmol/l in a 90-min incubation. Morphine and DAME were rather more effective than Leu5-enkephalin, possibly because of degradation of the latter. Naloxone reversed the effect of morphine. All three opiates showed little effect on dopamine-inhibited prolactin secretion in a perifusion system. The data accord with previous suggestions that prolactin secretion may be stimulated both by very low concentrations of dopamine and by opiates acting to reverse the inhibition exerted by higher dopamine concentrations. It should be noted that both morphine and the enkephalins have similar effects on prolactin secretion, despite their normal specificity for different opiate receptors; their actions on the pituitary may thus be rather non-specific. J. Endocr. (1986) 109, 313–320


2012 ◽  
Vol 24 (5) ◽  
pp. 704 ◽  
Author(s):  
Constanza M. López-Fontana ◽  
María E. Maselli ◽  
Ana M. Salicioni ◽  
Rubén W. Carón

Lactogenesis is a very complex process highly dependent on hormonal regulation. In the present study the time-course of the inhibitory actions of progesterone on prolactin secretion, mammary gland morphology and lactogenesis from mid- to late gestation in rodents was investigated. Groups of pregnant rats were luteectomised or administered with mifepristone on Day 10, 13, 15 or 17 of gestation and decapitated 28 or 48 h later. Whole-blood samples and the inguinal mammary glands were taken for determinations of hormone levels and for measurement of mammary content of casein and lactose and for tissue morphology analyses, respectively. Luteectomy or mifepristone evoked prolactin increases only after Day 17 of gestation. Mammary content of casein was increased by both treatments regardless of timing or duration. Mifepristone was less effective than luteectomy in inducing lactose production and the effect was only observed after Day 15 of gestation. Analysis of mammary gland morphology confirmed the observed effect of progesterone on lactogenesis. Both treatments triggered remarkable secretory activity in the mammary gland, even without a parallel epithelial proliferation, demonstrating that the mammary epithelium is able to synthesise milk compounds long before its full lobulo–alveolar development is achieved, provided that progesterone action is abolished. Thus, the present study demonstrates that progesterone is a potent hormonal switch for the prolactin and prolactin-like effects on mammary gland development and its milk-synthesising capacity during pregnancy, and that its inhibitory action is already evident by mid-pregnancy in rodents.


The Auk ◽  
1987 ◽  
Vol 104 (2) ◽  
pp. 208-217 ◽  
Author(s):  
Eve S. Hiatt ◽  
Arthur R. Goldsmith ◽  
Donald S. Farner

Abstract Plasma concentrations of prolactin, LH, and FSH were measured in free-living pairs of Zonotrichia leucophrys pugetensis throughout the natural breeding season, and during a photoperiodically induced cycle of gonadal development and regression in both sexes of captive Z. l. gambelii under controlled conditions. In free-living male Z. l. pugetensis plasma levels of FSH, which correlate well with changes in testicular weight reported previously, are higher than in females. Although only females of this species incubate, maximal levels of prolactin are observed in both sexes during late incubation. This is consistent with observations in other avian species and suggestive of a role for prolactin in incubation and associated parental behavior. The temporal association of elevated FSH with high levels of prolactin in females may represent a mechanism for maturation of ovarian follicles for the next clutch in this race, which typically raises as many as 3 broods per season. In the laboratory study on Z. l. gambelii, prolactin secretion in both sexes appears to have been induced photoperiodically in the absence of other environmental stimuli associated with incubation. The time course and magnitude of plasma prolactin levels were similar in both sexes, although levels were considerably lower than values obtained from incubating birds during the field study. Plasma levels of LH and FSH in females increased rapidly in response to photostimulation and began to decline after one week, whereas in males the pattern of increase and decrease of both gonadotropins was more gradual.


2006 ◽  
Vol 111 (2) ◽  
pp. 145-151 ◽  
Author(s):  
Indika Edirisinghe ◽  
Kellie McCormick Hallam ◽  
C. Tissa Kappagoda

The metabolic syndrome, Type II (non-insulin-dependent) diabetes and obesity are associated with endothelial dysfunction and increased plasma concentrations of NEFAs (non-esterified fatty acids; free fatty acids). The present study was undertaken to define the inhibitory effects of saturated NEFAs on EDR (endothelium-dependent relaxation). Experiments were performed in rings of rabbit aorta to establish (i) dose–response relationships, (ii) the effect of chain length, (iii) the effect of the presence of double bonds, (iv) reversibility and time course of inhibition, and (v) the effect on nitric oxide production. Aortic rings were incubated (1 h) with NEFA–albumin complexes derived from lauric (C12:0), myristic (C14:0), palmitic (C16:0), stearic (C18:0) and linolenic (C18:3) acids. EDR induced by acetylcholine (0.1–10 μmol/l) was measured after pre-contraction with noradrenaline. Inhibition of EDR was dose-dependent (0.5–2 mmol/l NEFA), and the greatest inhibition (51%) was observed with stearic acid (2 mmol/l). Lauric acid had the smallest inhibitory effect. The inhibitory effects were always reversible and were evident after 15 min of incubation. Linolenic acid caused a significantly lower inhibition of EDR than stearic acid. SOD (superoxide dismutase) restored the inhibitory effect caused by NEFAs, suggesting the involvement of ROS (reactive oxygen species) in removing nitric oxide. The nitric oxide concentration measured after exposure of the rings to acetylcholine was lower after incubation with NEFAs than with Krebs buffer alone. This finding is consistent with removal of nitric oxide by ROS. This claim was supported by the demonstration of increased concentrations of nitrated tyrosine in the rings incubated with NEFAs.


1991 ◽  
Vol 131 (2) ◽  
pp. 245-250 ◽  
Author(s):  
Y. D. Li ◽  
Z. W. Zhang ◽  
W. X. Li

ABSTRACT The effect of transferrin on basal and FSH-stimulated aromatase activity of granulosa cells from immature female rats treated with diethylstilboestrol (DES) was examined in vitro by a radiometric method. The basal activity of the enzyme was very low after 3 days of incubation. Treatment with FSH (20 ng/ml) resulted in a 9·6-fold increase in activity, whereas coincubation with increasing doses of transferrin (3–300 μg/ml) produced a dose-dependent inhibition of FSH-stimulated aromatase activity with a projected minimal effective dose of < 2 μg/ml. A time-course study showed that the inhibitory effect of transferrin on aromatase activity has become significant at 48 h of incubation. The inhibitory action of transferrin on the enzyme complex was further confirmed by showing that the FSH dose–response curve was significantly suppressed by concomitant treatment with 100 μg transferrin/ml with a maximum suppression of 54·1 % at a dose of 30 ng FSH/ml. The possibility that transferrin may act through a non-specific inhibitory effect seems unlikely, as no changes in cell number and DNA content per well were observed. In fact, protein synthesis was enhanced after treatment with transferrin. Aromatase activity, stimulated by several promoters of cyclic AMP (cAMP), such as prostaglandin E2 (PGE2), forskolin and 8-bromo-cAMP, was significantly suppressed by 100 μg transferrin/ml (36·6, 47·4 and 23·4% inhibition respectively), suggesting that the effect of transferrin on FSH action may involve a site(s) distal to cAMP generation. These findings indicated that transferrin, present in follicular fluid, may play an important role in the regulation of granulosa cell differentiation. Journal of Endocrinology (1991) 131, 245–250


Reproduction ◽  
2000 ◽  
pp. 151-156 ◽  
Author(s):  
E Diaz ◽  
D Pazo ◽  
AI Esquifino ◽  
B Diaz

The effect of age and melatonin on the activity of the neuroendocrine reproductive system was studied in young cyclic (3-5 months-old), and old acyclic (23-25 month-old) female rats. Pituitary responsiveness to a bolus of GnRH (50 ng per 100 g body weight) was assessed at both reproductive stages in control and melatonin-treated (150 micrograms melatonin per 100 g body weight each day for 1 month) groups. After this experiment, female rats were treated for another month to study the influence of ageing and melatonin on the reproductive axis. Plasma LH, FSH, prolactin, oestradiol and progesterone were measured. A positive LH response to GnRH was observed in both control groups (cyclic and acyclic). However, a response of greater magnitude was observed in old acyclic rats. Melatonin treatment reduced this increased response in acyclic rats and produced a pituitary responsiveness similar to that of young cyclic rats. FSH secretion was independent of GnRH administration in all groups, indicating desynchronization between LH and FSH secretion in response to GnRH in young animals and during senescence. No effect on prolactin was observed. Significantly higher LH (3009.11 +/- 1275.08 pg ml(-1); P < 0.05) and FSH concentrations (5879.28 +/- 1631.68 pg ml(-1); P < 0.01) were seen in acyclic control rats. After melatonin treatment, LH (811.11 +/- 89.71 pg ml(-1)) and FSH concentrations (2070 +/- 301.62 pg ml(-1)) decreased to amounts similar to those observed in young cyclic rats. However, plasma concentrations of oestradiol and progesterone were not reduced. In conclusion, the results of the present study indicate that, during ageing, the effect of melatonin is exerted primarily at the hypothalamo-pituitary axis rather than on the ovary. Melatonin restored the basal concentrations of pituitary hormones and pituitary responsiveness to similar values to those observed in young rats.


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