Differences in the Effects of Acute and Chronic Administration of Dexfenfluramine on Cortisol and Prolactin Secretion

The possibility that chronic hyperprolactinaemia results in loss of the ability of hypothalamic dopamine activity to inhibit prolactin secretion was studied in rats. Two degrees of hyperprolactinaemia (moderate and gross) were induced in the animals following the chronic administration of two different doses of oestradiol valerate. In rats with high chronic serum prolactin concentrations (approximately 20 times normal) there was a profound increase in prolactin secretion following inhibition of brain dopamine (DA) synthesis by 3-iodo-L-tyrosine, indicating intact and highly active hypothalamic DA-inhibitory control of prolactin release. However, the degree of hypothalamic inhibition of prolactin release relative to normal controls was significantly reduced. In animals with grossly elevated chronic serum prolactin concentrations (approximately 100 times normal) a prolactin response to DA synthesis inhibition was absent despite a highly significant reduction in hypothalamic DA concentrations induced by 3-iodo-L-tyrosine. These observations show that chronic and gross hyperprolactinaemia in the rat results in loss of hypothalamic DA inhibitory control of prolactin secretion. The use of 3-iodo-L-tyrosine to block brain DA synthesis in these studies has provided significant new data relating to prolactin control in hyperprolactinaemic states and indicates that this compound could be a useful clinical tool in the study of human hyperprolactinaemia.

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Effects of cyclosporine at the hypothalamic-pituitary axis in pituitary-grafted young female rats

Journal of Endocrinology ◽

10.1677/joe.0.1440159 ◽

1995 ◽

Vol 144 (1) ◽

pp. 159-164 ◽

Cited By ~ 18

Author(s):

A I Esquifino ◽

M L Moreno ◽

A Arce ◽

C Agrasal ◽

J Pérez-Díaz ◽

...

Keyword(s):

Pituitary Gland ◽

Chronic Administration ◽

Young Female ◽

Prolactin Secretion ◽

Female Rats ◽

Plasma Prolactin ◽

Serotonin Content ◽

Dihydroxyphenylacetic Acid ◽

Hypothalamic Pituitary Axis

Abstract This work was designed to investigate the effects of cyclosporine on prolactin secretion by an ectopically grafted heterologous pituitary gland, and on the hypothalamic content of norepinephrine, dopamine and serotonin. The administration of cyclosporine prevented the augmentation in plasma prolactin levels which occurred following an ectopic graft of a litter-mate pituitary gland. In contrast, in sham-operated rats, cyclosporine increased prolactin levels on day 8 of treatment. Both pituitary grafting and cyclosporine treatment in sham-operated rats decreased hypothalamic norepinephrine content. In grafted rats, cyclosporine returned hypothalamic norepinephrine to normal. Hypothalamic serotonin content decreased 8 days after pituitary grafting but increased to the values of control animals after cyclosporine administration. Cyclosporine treatment for 2 and 8 days increased serotonin content in sham-operated animals. As expected, the hypothalamic dihydroxyphenylacetic acid/dopamine index increased after pituitary grafting and administration of cyclosporine for 8 days resulted in a further increase. Cyclosporine administration for 2 days, however, decreased this index to the values observed in control animals while drug treatment of control rats for 8 days decreased the dihydroxyphenylacetic acid/dopamine index. In vitro release of prolactin from the ectopic gland was markedly decreased in animals treated with cyclosporine for 2 days and this effect was less evident in 8-day treated rats. These data suggest that the impairment of the local immune reaction after pituitary grafting, by cyclosporine administration for 2 days, prevents the augmentation of plasma prolactin levels and normalizes the hypothalamic catecholamine parameters, thus suggesting that the effects of cyclosporine at the hypothalamo-pituitary axis are exerted through changes in prolactin secretion by the graft, although chronic administration of cyclosporine may also have a direct effect on the hypothalamus. Journal of Endocrinology (1995) 144, 159–164

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Influence of chronic administration of L-dopa on movement-related desynchronization pattern preceding voluntary movement in Parkinson's disease

Electroencephalography and Clinical Neurophysiology ◽

10.1016/s0013-4694(97)88709-7 ◽

1997 ◽

Vol 103 (1) ◽

pp. 154

Author(s):

L Defebvre

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Voluntary Movement ◽

Chronic Administration

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Antinociceptive effect of chronic administration of green tea epigallocatechin gallate in a model of diabetic hyperalgesia in rat

Planta Medica ◽

10.1055/s-0031-1282866 ◽

2011 ◽

Vol 77 (12) ◽

Author(s):

T Baluchnejadmojarad ◽

M Roghani

Keyword(s):

Green Tea ◽

Antinociceptive Effect ◽

Epigallocatechin Gallate ◽

Chronic Administration

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Ridogrel Inhibits Systemic and Renal Formation of Thromboxane A2 and Antagonizes Platelet Thromboxane A2/Prostaglandin Endoperoxide Receptors upon Chronic Administration to Man

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656351 ◽

1992 ◽

Vol 68 (02) ◽

pp. 214-220 ◽

Cited By ~ 5

Author(s):

C Weber ◽

J R Beetens ◽

F Tegtmeier ◽

P Van Rooy ◽

E Vercammen ◽

...

Keyword(s):

Uric Acid ◽

Potent Inhibitor ◽

Ex Vivo ◽

Thromboxane A2 ◽

Chronic Administration ◽

Response Curves ◽

Clinically Significant ◽

Synthase Inhibitor ◽

The Right ◽

Steady State Plasma Level

SummaryThe effects of ridogrel, a dual thromboxane A2 (TXA2) synthase inhibitor and TXA2/prostaglandin (PG) endoperoxide receptor antagonist, on systemic and renal production of prostaglandins and on platelet TXA2/PG endoperoxide receptors was evaluated upon chronic administration (300 mg b. i. d. orally, for 8 and 29 days) to man. Such a medication with ridogrel inhibits the systemic as well as the renal production of TXA2 as measured by the urinary excretion of 2,3-dinor-TXB2 and TXB2 respectively without inducing significant changes in systemic or renal PGI2 production. Simultaneously with the latter effects, the production of TXB2 by spontaneously coagulated whole blood ex vivo is inhibited (>99%) while that of PGE2 and PGF2α is largely increased. Administration of ridogrel causes a three- to five-fold shift to the right of concentration-response curves for U46619 in eliciting platelet aggregation; no tachyphylaxis is observed after 29 days of treatment in this respect. Apart from a reduction of serum uric acid levels with a concomitant increase in urinary uric acid excretion during the first days of treatment, no clinically significant changes in hematological, biochemical, hemodynamic and coagulation parameters occur during the 8 days or 29 days study. The study demonstrates that ridogrel is a potent inhibitor of the systemic as well as renal TXA2 synthase and an antagonist of platelet TXA2/PG endoperoxide receptor in man, covering full activity during 24 h at steady-state plasma level conditions without tachyphylaxis during 29 days of medication. The compound is well tolerated, at least during 1 month of administration.

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SPECIAL PROBLEMS IN TOXICITY TESTING OF LONG ACTING DEPOT CONTRACEPTIVES

Acta Endocrinologica ◽

10.1530/acta.0.075s315 ◽

1974 ◽

Vol 77 (1_Suppla) ◽

pp. S315-S354 ◽

Cited By ~ 4

Author(s):

F. Neumann ◽

R. von Berswordt-Wallrabe ◽

W. Elger ◽

K.-J. Gräf ◽

S. H. Hasan ◽

...

Keyword(s):

Biological Effects ◽

Histological Finding ◽

Toxicity Testing ◽

Prolactin Secretion ◽

List Type ◽

Human Species ◽

Prolactin Plasma Level ◽

Human Use ◽

Long Acting ◽

Reproductive Processes

ABSTRACT Two types of so-called "depot contraceptives", long-acting steroids which are of interest for human use, were studied in animals. Norethisterone oenanthate, mainly gestagenic in the human and other species, turned out to be predominantly oestrogenic in rats. This oestrogenicity caused indirectly, via an enhanced hypophysial prolactin secretion, the well-known hypophysial and mammary tumours in rats. Another synthetic gestagen, 4,6-dichloro- 17- acetoxy- 16α-methyl-4,6-pregnadiene-3,20-dione, which might be considered in its biological actions similar to preparations containing chlormadinone acetate or medroxy-progesterone acetate, induced no signs of oestrogenicity in dogs. It is surmised that its gestagenic influence indirectly, and probaby, via an enhanced hypophysial prolactin secretion caused "mammary nodules" in this "non-rodent" species. These studies have born out mainly two facts: A synthetic steroid, norethisterone oenanthate, exerted different biological effects in different species: it was a gestagen in the rabbit, whereas in rats, its predominant influence was oestrogenic. The hypophysial prolactin secretion was enhanced in various species by different mechanisms: in rats, the oestrogenicity caused an increased prolactin plasma level, whereas in dogs, a gestagen with obviously no inherent oestrogenicity, 4,6-dichloro-17-acetoxy-16α-methyl-4,6-pregnadiene-3,20-dione, converted the histological appearance of the anterior pituitary into a condition with a greatly increased number of eosinophils. This histological finding was interpreted as an indicator for a hypersecretion of prolactin. Hence, animal work with "gestagens" has only limited predictive value with respect to their possible effects in the human species. Therefore, inflexible recommendations are not helpful in solving the safety problem of long-acting steroids which affect primarily reproductive processes.

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