Dopamine D1, Dopamine D2 and Prolactin Receptors Expression


Dopamine D1, Dopamine D2, and Prolactin Receptor Messenger Ribonucleic Acid Expression by the Polymerase Chain Reaction in Human Meningiomas
Previous studies have suggested the presence of high-affinity dopamine D1 receptors and prolactin receptors in human cerebral meningiomas. In this study, using the polymerase chain reaction, we report the presence of the messenger ribonucleic acid (mRNA) for the dopamine D1 and D2 receptors and the prolactin receptor in meningioma tissue specimens and cell cultures derived from meningioma tissue. Dopamine D1 receptor mRNA was present in a majority of female tissue specimens and in all male tissue specimens. D2 receptor mRNA was detected in all specimens examined. Prolactin receptor mRNA was present in a little more than half of the female and male meningioma tumor specimens. The polymerase chain reaction products were directly sequenced to confirm the identity of these receptors in meningiomas and cell cultures. Ligand binding studies confirmed the presence of the dopamine D1 receptor in meningioma tissue specimens. In contrast, receptor studies with the dopamine D2 ligand [125I]4-iodospiperone failed to detect D2 binding in meningioma membrane preparations. These results suggest the existence of active dopamine D1 receptors in cerebral meningiomas.

Carroll RS, Schrell UMH, Zhang J, Dashner K, Nomikos P, Fahlbusch R, Black PM.  Dopamine D1, Dopamine D2, and Prolactin Receptor Messenger Ribonucleic Acid Expression by the Polymerase Chain Reaction in Human Meningiomas .  Neurosurgery, 1996; 38:2: 376-375.



Regulation of Secretion of PTHrP by Ca(2+)-sensing Receptor in Human Astrocytes, Astrocytomas, and Meningiomas
We report the isolation by RT-PCR of partial cDNAs encoding the human peroxisome proliferator-activated receptor (PPAR) isoforms PPARbeta and -gamma in human primary astrocytes (HPA) as well as in the human malignant astrocytoma cell line T98G. In contrast, we failed to detect PPARalpha mRNA in either of these two cell types. Because PPARbeta is ubiquitously expressed but has, as yet, no known function, we pursued our functional studies of these cells with regard to PPARgamma. To that end, we showed that PPARgamma protein is abundantly expressed in both cell types, having a molecular weight of approximately 50 kDa. Immunocytochemistry revealed a predominantly nuclear localization of this receptor. Moreover, incubation of the two cell types with 1-12 mcM 15-deoxy PGJ(2) or 1-12 mcM ciglitazone, both of which are agonists of PPARgamma, induced loss of cellular viability as assessed by the MTT assay after a 4 hr incubation. Reduced cellular viability as a consequence of exposure to PGJ(2) or ciglitazone resulted from induction of apoptosis, as assessed by DNA fragmentation and Hoechst staining, and involves activation of the CPP32 (caspase-3) protease. These data show that modulation of the process of apoptosis is one function of PPARgamma in cells derived from the human astrocytic lineage. Copyright 2000 Wiley-Liss, Inc.

Chattopadhyay N, Evliyaoglu C, Heese O, Carroll R, Sanders J, Black P, Brown EM.  Regulation of Secretion of PTHrP by Ca(2+)-sensing Receptor in Human Astrocytes, Astrocytomas, and Meningiomas .  Am J Physiol Cell Physiol, 279(3): C691-C699, 2000.



The importance of dopamine in the pathogenesis of experimental prolactinomas
The factors responsible for the production of prolactin-secreting tumors are obscure. One hypothesis, that chronic loss of dopamine control from the hypothalamus may be associated with prolactinoma formation, was tested. Female adult Fischer 344 rats were subjected to ovariectomy and were then given subcutaneous implants of diethylstilbestrol (DES) Silastic capsules to produce lactotrophic hyperplasia. Sequential studies assessed the neuronal activity of the tuberoinfundibular dopaminergic neurons of the arcuate nucleus of the hypothalamus (A12) during and after this estrogen-induced pituitary growth. Immunocytochemical staining for tyrosine hydroxylase was used as a marker for dopamine synthesis, plasma radioimmunoassay provided plasma prolactin levels, and magnetic resonance imaging and histological studies were performed to examine the structural changes occurring in the pituitary gland. Animals were sacrificed from 3 to 67 days after DES implantation. To determine the reversibility of the estrogen-induced changes, rats were also sacrificed at different time intervals after the removal of 30-, 40-, or 60-day DES implants. After 30 days of DES treatment, plasma prolactin levels increased 40-fold and pituitary weight increased more than threefold. Tyrosine hydroxylase immunoreactivity diminished gradually and was almost completely depleted at 30 days. Pituitary histology revealed marked prolactin cell hyperplasia. These changes were completely reversible; removal of the capsule after 30 days resulted in eventual normalization of plasma prolactin levels and pituitary size and in restoration of tyrosine hydroxylase immunoreactivity in the A12 region. Sixty days of DES treatment produced large hemorrhagic tumors with sustained high plasma prolactin levels and an irreversibly distorted A12 area. These observations suggest that in these animals loss of dopamine regulation secondary to estrogen stimulation initially produces prolactin hyperplasia but that prolonged loss leads to adenoma formation.

El-Azouzi M, Hsu DW, Black PM, Jolesz F, Hedley-Whyte ET, Klibanski A, Zervas NT.  The importance of dopamine in the pathogenesis of experimental prolactinomas .  J Neurosurg, 72(2): 273-281, 1990.


Dopaminergic regulation of alpha-subunit secretion and messenger ribonucleic acid levels in alpha-secreting pituitary tumors
Glycoprotein hormone and/or subunit secretion has been increasingly recognized in patients with pituitary nonsecretory adenomas and alpha-subunit secretion has been reported to occur in 5-10% of all pituitary tumors. We investigated the dopaminergic regulation of alpha-subunit secretion in four patients with alpha-subunit secreting pituitary adenomas documented by serum and immunocytochemical studies. In three of the four patients there was a significant decrease in serum alpha-subunit concentrations during 6 weeks of bromocriptine administration. Tumor size decreased in two patients. In pituitary tumor cells from one patient cultured in vitro, dopamine caused a highly significant decrease in media alpha-subunit concentrations. To investigate whether dopaminergic regulation of alpha-subunit secretion occurs at a pre- or posttranslational level, messenger RNA (mRNA) from cultured tumor cells from one patient was analyzed by Northern blot techniques. A decrease in alpha-subunit mRNA occurred in cells incubated with 10(-10), 10(-8), and 10(-6) M dopamine. We conclude that dopamine suppressed pituitary tumor alpha-subunit secretion and mRNA levels. Dopamine agonists may be of benefit in the therapy of patients with such tumors.

Klibanski A, Shupnik MA, Bikkal HA, Black PM, Kliman B, Zervas NT .  Dopaminergic regulation of alpha-subunit secretion and messenger ribonucleic acid levels in alpha-secreting pituitary tumors .  J Clin Endocrinol Metab 66(1): 96-102, 1988.