DIRECT ANTIPROLIFERATIVE EFFECT OF DOPAMINE AGONISTS ON THE ANTERIOR PITUITARY GLAND IN ORGAN CULTURE

1978 ◽  
Vol 79 (2) ◽  
pp. 245-246 ◽  
Author(s):  
M. PAWLIKOWSKI ◽  
J. KUNERT-RADEK ◽  
H. STĘPIEŃ

Department of Experimental Endocrinology, Institute of Endocrinology, Medical Academy of Łódź, Dr Sterling sir. 3, 91–425 Łódź, Poland (Received 22 May 1978) Lloyd, Meares & Jacobi (1975) observed inhibition of mitotic activity in the anterior pituitary gland by the dopamine receptor agonist, bromocriptine, in oestrogen-treated male rats. This observation has been confirmed in our laboratory (Stępień, Wolaniuk & Pawlikowski, 1978). Suppression of mitotic activity in the pars intermedia of the rat pituitary gland by bromocriptine has also been observed (Rychter & Stępień, 1977). Furthermore, it has been found that the dopamine receptor blocker, pimozide, enhances mitotic activity in the rat anterior pituitary gland (Stępień et al. 1978). By the use of various ergot alkaloids, MacLeod & Lehmeyer (1973) succeeded in inhibiting the growth of transplantable rat pituitary tumours. There have also been observations suggesting an antiproliferative effect of bromocriptine on human pituitary tumours (Wass, Thorner, Morris, Rees, Mason, Jones &

1995 ◽  
Vol 145 (1) ◽  
pp. 43-49 ◽  
Author(s):  
J M M Rondeel ◽  
W Klootwijk ◽  
E Linkels ◽  
G A C van Haasteren ◽  
W J de Greef ◽  
...  

Abstract TRH-like peptides share the N- and C-terminal amino acids with TRH (pGlu-His-Pro-NH2) but differ in the middle amino acid residue. One of them, pGlu-Glu-Pro-NH2 (<EEP-NH2; EEP) is present in the rat pituitary gland, but its biological significance is unknown. We investigated the localization and regulation of this tripeptide in the rat pituitary gland. To distinguish between TRH and EEP two antisera were used for RIA: specificity of antiserum 4319 for the TRH-like peptides pGlu-Phe-Pro-NH2 and EEP was equal to or greater than that for TRH, whereas antiserum 8880 is TRH-specific. Our RIA data showed the presence of a TRH-like peptide in the anterior pituitary gland (AP) and of TRH in the posterior pituitary gland (PP). The TRH-like peptide in the AP was identified on anion-exchange chromatography and subsequent HPLC as EEP. Pathophysiological conditions such as altered thyroid and adrenal status and suckling did not affect pituitary gland levels of EEP. In general, however, there is a clear sex difference: levels of EEP are higher in male than in female rats. In both sexes gonadectomy leads to a substantial two- to threefold rise in EEP levels, abolishing the sex difference. Testosterone administration to gonadectomized male rats normalizes levels of EEP again. Disulfiram, an inhibitor of the enzyme peptidylglycine α-amidating monooxygenase, reduced levels of EEP in the AP by approximately 50%. In conclusion: 1) the TRH-like peptide EEP is present in the AP, whereas TRH is confined to the PP, 2) levels of EEP in the AP are regulated by sex steroids, 3) EEP is actively amidated in the AP and thus seems to be produced from a glycine-extended progenitor sequence. Journal of Endocrinology (1995) 145, 43–49


1977 ◽  
Vol 75 (3) ◽  
pp. 443-444 ◽  
Author(s):  
J. RYCHTER ◽  
H. STEPIEŃ

Department of Experimental Endocrinology, Institute of Endocrinology, Medical Academy of Łódź, Dr. Sterling str. 3, 91-425 Łódź, Poland (Received 31 May 1977) The secretory function of the intermediate lobe of the pituitary gland is under hypothalamic control (Howe, 1973; Hadley & Bagnara, 1975). Penny, Thody, Tilders & Smelik (1977) have suggested that the synthesis and release of melanocyte-stimulating hormone (MSH) is mediated by dopaminergic neurones which make synaptic contact with secretory cells in the pars intermedia (Björklund, Moore, Nobin & Stenevi, 1973). We have attempted to examine whether the dopaminergic mechanism is also involved in the control of the mitotic activity of the pars intermedia cells and have studied the effects of pimozide, a dopamine receptor blocker (Anden, Butcher, Corrodi, Fuxe & Ungerstedt, 1970) and 2-bromo-α-ergocriptine (bromo-criptine), a dopamine receptor agonist (Loew, Vigouret & Jaton, 1976) on the mitotic activity of the pars intermedia of the rat pituitary gland. Twenty-three


1986 ◽  
Vol 108 (3) ◽  
pp. 399-403 ◽  
Author(s):  
R. L. Pérez ◽  
G. A. Machiavelli ◽  
M. I. Romano ◽  
J. A. Burdman

ABSTRACT Relationships among the release of prolactin, the effect of oestrogens and the proliferation of prolactin-secreting cells were studied under several experimental conditions. Administration of sulpiride or oestradiol released prolactin and stimulated cell proliferation in the anterior pituitary gland of adult male rats. Clomiphene completely abolished the rise in cell proliferation, but did not interfere with the sulpiride-induced release of prolactin. Treatment with oestradiol plus sulpiride significantly increased serum prolactin concentrations and the mitotic index compared with the sum of the stimulation produced by both drugs separately. Bromocriptine abolished the stimulatory effect of oestradiol on the serum prolactin concentration and on cell proliferation. In oestradiol- and/or sulpiride-treated rats, 80% of the cells in mitoses were lactotrophs. The remaining 20% did not stain with antisera against any of the pituitary hormones. The number of prolactin-secreting cells in the anterior pituitary gland significantly increased after the administration of oestradiol or sulpiride. The results demonstrate that treatment with sulpiride and/or oestradiol increases the proliferation and the number of lactotrophs in the anterior pituitary gland of the rat. J. Endocr. (1986) 108, 399–403


1983 ◽  
Vol 97 (1) ◽  
pp. 65-74 ◽  
Author(s):  
J. A. Burdman ◽  
M. T. Calabrese ◽  
R. M. MacLeod

Hyperprolactinaemia produced in rats by the transplanted prolactin-secreting tumours MtTW15 and 7315a significantly (P<0·01) inhibited by 70% the incorporation of [3H]thymidine into the pituitary DNA of the host animals. The weight and the DNA content of the glands were significantly (P<0·01) reduced by 30%. The administration of haloperidol, a dopamine receptor blocking agent, to the tumour-bearing rats increased the suppressed DNA replication in the anterior pituitary glands by approximately 560% in the MtTW15-bearing rat and by 100% in the 7315a-bearing animals. Furthermore, injection of drugs which stimulate prolactin release either by blocking the synthesis of dopamine (α-methyl-p-tyrosine) or the re-uptake of dopamine (reserpine) stimulated DNA synthesis by 800 and 100% respectively in the anterior pituitary gland of rats bearing the MtTW15 tumour. In contrast, lisuride, a dopamine agonist, significantly inhibited the incorporation of [3H]thymidine into the DNA of the pituitary gland of normal but not hyperprolactinaemic rats. Chronically administered oestrogens to hyperprolactinaemic rats increased the weight (100%), DNA content (31%), incorporation of [3H]thymidine into DNA (680%) and synthesis and release of prolactin (300%) in the pituitary gland. The incorporation of [3H]thymidine into tumour DNA was several times higher than in the pituitary gland of the host animal and was not significantly modified by any of the above treatments. Likewise the hyperprolactinaemia of the tumour-bearing rats was not significantly changed. In conclusion, we have shown that hyperprolactinaemia inhibits DNA synthesis in the anterior pituitary gland and this inhibition can be reversed completely by a dopamine receptor blocking agent and by hypothalamic dopamine depleting drugs. We propose that dopamine regulates, either directly or indirectly, DNA synthesis in the lactotrophs of the pituitary gland, which may be responsive to negative feedback mechanisms.


1983 ◽  
Vol 96 (3) ◽  
pp. 395-400 ◽  
Author(s):  
S. W. J. Lamberts ◽  
E. G. Bons ◽  
P. Uitterlinden ◽  
W. H. Hackeng

Cyproheptadine and its metabolite desmethylcyproheptadine were shown to suppress directly the release of adrenocorticotrophin (ACTH) and β-lipotrophin/β-endorphin activity from the neurointermediate lobe of the pituitary gland incubated in vitro. Neither compound affected the release of ACTH from the anterior pituitary gland. Serotonin stimulated the release of ACTH and β-lipotrophin/β-endorphin activity from the neurointermediate lobe, but did not influence the (desmethyl)cyproheptadine-mediated inhibition of hormone release. These results indicate that serotonin and cyproheptadine affect hormone release by the neurointermediate lobe by a direct action. The effect of cyproheptadine, however, might not be exerted by a serotonin receptor.


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