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Pain treatment in metastatic prostatic carcinoma by radiofrequency thermolesion on the pituitary gland. Preliminary report.

Radiofrequency thermolesion on the pituitary gland is a simple and safe procedure to reduce pain in metastatic prostatic carcinoma. The method is indicated in patients with multiple and bilateral painful areas due to bone metastases, which are resistant to hormonal therapy and Estracyt. A good pain relief is achieved in over 60% of patients. Only one infectious complication has been encountered in a series of 17 patients treated this way.

Electrocoagulation↗

Nuclear estradiol and cytosol progestin receptor concentrations in the brain and the pituitary gland and sexual behavior in ovariectomized estradiol-treated middle-aged rats.

We wished to determine whether the altered nuclear estradiol (E2) receptor concentrations in middle-aged rats can explain the diminished responsiveness to E2 observed in aging rats. Therefore, we measured receptor concentrations in various brain areas and the pituitary gland of young and middle-aged ovariectomized rats 2 and 4 days after implantation of Silastic capsules containing E2. To determine whether any observable changes had physiological consequences, we correlated age-dependent changes in E2 nuclear receptor concentrations with two E2-dependent parameters: cytosol progestin receptor levels in equivalent brain areas and pituitary gland and progesterone-facilitated reproductive behaviors. Young (3-4 months old) and middle-aged (10-12 months old) Sprague-Dawley rats were ovariectomized and received Silastic capsules containing E2 dissolved in oil 1 week later (day 0). Groups of rats were killed at 1200 h on either day 2 or day 4. Nuclear E2 and cytosol progestin receptor concentrations were assessed in a nuclear and cytoplasmic extract from the medial basal hypothalamus, preoptic area, amygdala, and pituitary gland. To test steroid-induced mating behavior, ovariectomized young and middle-aged rats were treated with E2-containing capsules for 2 or 4 days. At 0900 h progesterone (0.2 mg/kg BW) was injected sc and receptive and proceptive behaviors were observed when experienced males were introduced 4-6 h later. Two days after implantation of E2 capsules, middle-aged rats exhibited lower nuclear E2 receptor concentrations in the medial basal hypothalamus and preoptic area than young rats. By day 4, there were no significant age-related differences in any brain area or in the pituitary gland. Parallel age-related differences were observed in cytosol progestin receptor concentrations on day 2 but they were not evident by day 4. Similarly, middle-aged rats exhibited deficits in proceptive behavior, lordosis quotient, and lordosis quality score on day 2, but there were no differences compared to young rats on day 4. These data demonstrate that E2-induced nuclear E2 receptor concentrations are lower in selected areas of the brain of middle-aged rats. Such changes appear to be physiologically important because they are correlated with changes in E2-induced cytosol progestin receptor concentrations and steroid-induced behaviors. Furthermore, they may partially account for age-related differences in E2-induced LH surges on day 2.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Progesterone inhibits prolactin and growth hormone release from fowl pituitary glands in vitro.

After preincubation of anterior pituitary glands of broiler fowls for 20 h in either medium alone or medium containing progesterone, their responsiveness to hypothalamic stimulation and to thyrotrophin releasing hormone (TRH) was determined. Following exposure to progesterone the basal rate of release of prolactin was reduced in a concentration-related manner but basal growth hormone release was unaffected. Stimulation of the release of prolactin and growth hormone by both hypothalamic extract and TRH was reduced following incubation with progesterone, and the reduction of the prolactin response to TRH was related to progesterone concentration.

Animals↗

Receptor autoradiographic analysis of insulin-like growth factor-I (IGF-I) binding sites in rat forebrain and pituitary gland.

1. Specific 125I-labeled insulin-like growth factor-I [( 125I] IGF-I) binding sites in the rat forebrain and pituitary gland were investigated using quantitative receptor autoradiography. 2. High densities of [125I]IGF-I binding sites were present in the olfactory nerve layer, olfactory glomerular layer, choroid plexus, CA3 and CA4 of the hippocampus, basolateral amygdaloid nucleus, and endopiriform nucleus. Moderate to high binding densities were found in the cerebral cortex (II, VI), bed nucleus stria terminalis, accumbens nucleus, lateral septum, median preoptic nucleus, supraoptic nucleus, paraventricular hypothalamic nucleus, and ventroposterior thalamic nucleus. In the circumventricular organs, subfornical organ, vascular organ of the lamina terminalis, and median eminence, the binding sites were numerous. High densities of [125I]IGF-I binding sites were also observed in the anterior pituitary gland. 3. In kinetic experiments, [125I]IGF-I binding sites in the olfactory glomerular layer, choroid plexus, median eminence, and anterior pituitary gland were found to be single and of a high affinity. 4. Noteworthy was the difference in the potency of insulin in inhibiting the binding among the areas examined, a finding which suggests heterogeneity of IGF-I receptors. 5. The possibility that IGF-I plays the role of a neurotransmitter and/or neuromodulator in the central nervous system warrants further investigation.

Animals↗

Renal cell carcinoma metastatic to the pituitary gland: clinical manifestations and successful treatment with transsphenoidal resection.

OBJECTIVE: To describe two cases of metastatic involvement of the pituitary gland by renal cell carcinoma (RCCA) and review the medical literature regarding this entity. METHODS: We present two case reports and discuss the published literature to illustrate the clinical findings, radiographic features, and recommended management of RCCA metastatic to the pituitary gland. RESULTS: During a 12-month period, we encountered two patients, one with visual deficits and both with anterior pituitary dysfunction, who had large sellar lesions that were histologically proved to be RCCA. Both patients were successfully treated with transsphenoidal surgical resection of the lesion, one of whom is alive and well more than 2 years later. A pituitary metastatic tumor is an uncommon complication of RCCA; it may be difficult to diagnose and potentially fatal. Anterior pituitary dysfunction and visual disturbances are more common initial features than is diabetes insipidus, in contrast to pituitary metastatic involvement from other tumors. CONCLUSION: Transsphenoidal resection is a safe and effective method of treatment of RCCA metastatic to the pituitary gland.

Journal Article↗

Induction of cytosolic progestin binding sites by catecholestrogens in rat pituitary gland and uterus: different potencies of 2- and 4-hydroxyestradiol.

The ability of catecholestrogens to induce cytosolic progestin binding sites in the hypothalamus, pituitary gland, and uterus of ovariectomised-adrenalectomised rats was demonstrated by the increase in high-affinity [3H]promegestone binding sites (KD 1.39, 0.50, and 0.54 nM, respectively) following a single subcutaneous injection (26.4 micrograms/animal) of the 3.4-dibenzoate ester of 4-hydroxyestradiol. The affinity and the time course of induction of these binding sites were very similar to those after a single injection of an equivalent dose (20 micrograms/animal) of estradiol 3-benzoate, exhibiting maximal receptor levels after 44 h. Widely differing efficacies in the induction of progestin binding sites were observed between the dibenzoate esters of 2- and 4-hydroxyestradiol. 2-Hydroxyestradiol 2,3-dibenzoate was ineffective in the pituitary gland up to a dose of 132 micrograms/animal, whereas 4-hydroxyestradiol dibenzoate was equipotent to estradiol benzoate, showing a maximal induction of progestin binding sites at single doses in the range of 13.2-26.4 micrograms/animal (equivalent to 10-20 micrograms of estradiol benzoate). As compared to the pituitary gland, the uterus was much more sensitive to the systemic administration of estrogen benzoates. At single doses in the range of 1.32-6.6 micrograms/animal (equivalent to 1-5 micrograms of estradiol benzoate), 4-hydroxyestradiol dibenzoate induced maximal levels of progestin receptors, and even 2-hydroxyestradiol dibenzoate, when given at a high dose (132.4 micrograms/animal, equivalent to 100 micrograms of estradiol benzoate), produced a slight increase in progestin binding sites.

Adrenalectomy↗

Adrenocorticotropic hormone cells and immunoreactive beta-endorphin cells in the human pituitary gland: normal and pathologic conditions studied by the peroxidase-labeled antibody method.

The comparative immunohistochemical localization of adrenocorticotropic hormone (ACTH) and beta-endorphin-like immunoreactivity (referred to as beta-endorphin) was studied in 16 human anterior pituitary glands from 6 normal adults, 4 normal fetuses, 1 stillborn infant, 2 anencephalic infants, 1 adult with Crooke's hyaline degeneration, and 2 patients with pituitary adenomas associated with Cushing's syndrome. Mirror sections were used in order to enable precise comparison of the same cells on the two consecutive tissue sections. In these normal and pathologic human anterior pituitary glands, ACTH and beta-endorphin were mostly localized in the same cells. In the normal adult pituitary glands, however, some ACTH cells were negative for beta-endorphin; and in one of the pituitary adenomas, some tumor cells were positive for only one hormone (beta-endorphin). These data suggest concomitant production of ACTH and beta-endorphin in the same cells and support the production of precursor molecules for these two hormones. The significance of ACTH-positive, beta-endorphin-negative normal cells and beta-endorphin-positive, ACTH-negative tumor cells is also discussed.

Adenoma↗

The ternary complex model. Its properties and application to ligand interactions with the D2-dopamine receptor of the anterior pituitary gland.

Agonists and antagonists interact with the pituitary D2-dopamine receptor in a complex fashion that has been accounted for by proposing that the receptor exists in two interconvertible affinity states [De Lean et al., Mol. Pharmacol. 22:290-297 (1982)]. These two states appear to be modulated by guanine nucleotides such that the state existing in the presence of excess guanine nucleotide has low affinity for agonists and high affinity for antagonists. These observations, together with several lines of evidence from other laboratories, have suggested the interaction of the receptor with a guanine nucleotide-binding protein and a model describing the reversible interaction of the receptor (R) with an additional membrane component (X) was studied [De Lean et al., J. Biol. Chem. 255:7108-7117 (1980)]. Several properties of this ternary complex model are presented and discussed in terms of the interpretation of the analysis of simulated binding data using the mass-action model. Computer modeling of experimental binding data obtained from membrane homogenates of bovine anterior pituitary glands indicated that a ternary complex model will fit only under conditions where, in the absence of any ligand, there is a tight interaction or "precoupling" of R with X, with the latter being in stoichiometrically limiting amounts; antagonists and guanine nucleotides would tend to destabilize this interaction, whereas agonists would serve to stabilize the coupled form. These results, for a receptor system that inhibits adenylate cyclase activity, are notably different from those observed for the beta-adrenergic receptor, which stimulates the enzyme and may be a reflection of differences in the molecular mechanisms of the interaction of the two receptor systems with their ligands and their effector. Some features of the model are not compatible with the experimental data and have indicated the need to consider extensions of the model, in light of recent advancements in our understanding of these regulatory components. Our results stress the importance of verifying the properties of proposed models and of cautiously testing these proposed models by their direct application to experimental data.

Animals↗

A new approach to three-dimensional reconstructed imaging of hormone-secreting cells and their microvessel environments in rat pituitary glands by confocal laser scanning microscopy.

There has been considerable interest in the relationship between hormone- secreting endocrine cells and their microvessels in human pituitary gland. However, microcirculatory networks have rarely been studied in three dimensions (3D). This study was designed to visualize and to reveal the relationship between hormone-secreting endocrine cells and their microvessel environment in 3D, using rat pituitary glands under various (hyper/hypo) experimental conditions by confocal laser scanning microscopy (CLSM). Female adult Wistar rats were used after bilateral adrenalectomy or ACTH administration for 2 weeks. Clear 3D reconstructed images of ACTH cells, the microvessel network and counterstained nuclei were obtained at a maximal focus depth of 1 mm by CLSM without any background noise. In the hyperfunctional state, slender cytoplasmic processes of hypertrophic stellate ACTH cells frequently extended to the microvessels. In the hypofunctional state, ACTH cells appeared atrophic and round with scanty cytoplasm, and cytoplasmic adhesions to microvessel network patterns were inconspicuous. Therefore, 3D reconstructed imaging by CLSM is a useful technique with which to investigate the microvessel environment of hormone-secreting cells and has the potential to reveal dynamic hormone-secreting pathways.

Adrenalectomy↗

Immunohistochemical localization of S-100 protein in the pig pituitary gland.

Immunohistochemical localization of S-100 protein was studied in anterior, intermediate and posterior lobe of the pig pituitary gland. Two immunopositive cells for S-100 protein were identified: the folliculo-stellate cells (FSc) in the glandular lobes and the pituicytes in the neural lobe. In the anterior lobe, immunoreactive folliculo-stellate cells were scattered among secretory cells. In the area where the secretory cells form strands and follicle-like groups the positive cells were concentrated in groups. In the intermediate lobe, S-100 protein-positive cells were located sparsely among secretory cells and next to secretory follicles and the pituitary cleft. These FSc were more voluminous and displayed fewer cytoplasmic processes. In the neurohypophysis, positive reaction for S-100 protein was seen in the pituicytes. These cells were distributed singly or concentrated in groups. The distribution, and morphologic characteristics of the FSc in the glandular lobes and the pituicytes in the neural lobe in the pig indicate different origin of both S-100 protein-positive cells.

Animals↗

beta-Adrenergic stimulation of the release of ACTH- and LPH-related peptides from the pars intermedia of the rat pituitary gland.

The intermediate lobe of the rat pituitary gland produces a series of peptides related to ACTH and LPH. The spontaneous and isoproterenol-stimulated release of such peptides was studied during in vitro superfusion of rat neurointermediate lobes with Krebs-Ringer medium. Products released into the superfusion medium were quantified by direct measurement or after chromatography on Sephadex G-50. ACTH bioactivity was determined by use of adrenal cortical cell suspension assay. In addition, NH2-terminal ACTH, CO2H-terminal ACTH, alpha-MSH and beta-endorphin radioimmunoassays were used. The results show that 1. neurointermediate lobes of rats secret spontaneously various ACTH- and LPH-related peptides in amounts proportional to the amounts in which these peptides are found in extracts of the neurointermediate lobe; 2. the beta-adrenergic agonist, isoproterenol, stimulated the spontaneous release of various peptides, including alpha-MSH, ACTH, CLIP, glycosylated CLIP, and beta-endorphin-like peptides; 3. isoproterenol induced a dose-dependent (10(-9)-10(-7) M), parallel increase in the release of alpha-MSH and ACTH following similar time courses and showing identical EC50 values (about 10(-8)M). Although the spontaneous release of alpha-MSH and ACTH from rat neurointermediate lobes is not strictly coupled under the conditions used in this study, isoproterenol seems to affect the spontaneous release of these peptides to the same relative extent.

Adrenergic beta-Agonists↗

Granulated 'marginal cell layer' in the rat anterior pituitary gland.

A granulated 'marginal layer cell' was observed in the lining of Rathke's residual pouch of 5 and 10 day-old rat anterior pituitary glands. Immunohistochemistry was not employed to identify the precise function of these cells. However, the cytological characteristics of nearly all of the cells indicated that they resembled GH-secreting cells, with a few displaying morphological features of corticotrophs. In pituitary glands of 5-20 day-old rats, both ends of Rathke's residual pouch extended into the pars distalis at the site of transitional zone of this lobe and of the pars intermedia. The cells within the 'invading' residual pouch contained numerous microvilli. In the middle portion of the residual pouch, cavities lined by 'marginal layer cells' had numerous microvilli and were adjoined by junctional complexes. In the adult rat pituitary gland, there were no granulated cells in the 'marginal cell layer' and no invasion of the residual pouch into the anterior lobe. From these data the possible source of the follicle and of the folliculo-stellate cells in the anterior pituitary of the rat is proposed.

Animals↗

Alteration by thyrotrophin-releasing hormone of heterogeneous components associated with thyrotrophin biosynthesis in the rat anterior pituitary gland.

An influence of thyrotrophin-releasing hormone (TRH) on TSH heterogeneity in close association with de-novo biosynthesis was studied in rat anterior pituitary glands. Hemipituitary glands from adult male rats were incubated in Krebs-Henseleit-glucose media containing [3H]glucosamine and [14C]alanine for 3 and 6 h in the presence or absence of 10 ng TRH per ml. Fractions of TSH in the pituitary extracts were obtained using affinity chromatography coupled with an anti-rat TSH globulin. These TSH fractions were analysed by isoelectric focusing. The control pituitary glands were composed of four component peaks (isoelectric point (pI) 8.7, 7.8, 5.3 and 2.5) of [3H]glucosamine and [14C]alanine incorporated into TSH, and the amounts of radioactivity of these components were increased with the incubation time. Of these peaks, radioactive components of pI 8.7 coincided with the non-radioactive TSH components measured by radioimmunoassay. Addition of TRH increased incorporation of [14C]alanine into TSH in each of the components to a greater extent than that of [3H]glucosamine. In addition, new components with pI 7.2, 6.5 and 6.2, each component corresponding to each unlabelled TSH component, were demonstrated in the presence of TRH. Because addition of TRH did not change the amounts of [14C]alanine-labelled TSH in the media, the newly formed components were assumed to be connected with protein synthesis occurring in the anterior pituitary gland, which may be specific substances in response to TRH administration. These results indicate that TRH principally elicits an increase in protein synthesis in TSH at the anterior pituitary level, resulting in an alteration of TSH heterogeneity.

Alanine↗

Decrease of LRH receptors in the pituitary gland in streptozotocin-induced diabetic rats.

In studies into the mechanism of anovulation in the diabetic condition, the LRH receptor content of the pituitary gland of rats with diabetes mellitus was determined. Normal female rats weighing 180-200 g were injected iv with either streptozotocin (6 mg/100 g body weight) or vehicle in dioestrus of the oestrous cycle. The rats were sacrificed by decapitation 9 days after treatment, and serum LH concentrations and the LRH content of the medial basal hypothalamus (MBH) were measured by radioimmunoassay (RIA), and the LRH receptor content of the pituitary gland was determined. The serum concentration of LH and the LRH content of the MBH in diabetic rats were 34.4 +/- 4.8 ng/ml (mean +/- SEM) and 2.05 +/- 0.04 ng/MBH, respectively, which were similar to the respective values of normal rats in dioestrus. However, the LRH receptor content of diabetic rats (13.2 +/- 3.9 fmol/pituitary) was significantly (P less than 0.05) lower than that of normal rats in dioestrus (68.0 +/- 7.1 fmol/pituitary) and pro-oestrus (59.4 +/- 13.6 fmol/pituitary). These results suggest that anovulation in diabetic rats is at least partly attributable to a low content of LRH receptors in the pituitary gland.

Animals↗

The effects of histidyl-proline-diketopiperazine, a metabolite of TRH, on prolactin release by the rat pituitary gland in vitro.

The effect of four different preparations of histidyl-proline-diketopiperazine (DKP) on prolactin (PRL) release by rat hemipituitary glands and cultured dispersed normal pituitary cells was studies. Three DKP preparations )0.1-1 micrometer) were ineffective on PRL release in vitro. By combining the results from 12 incubation vials in 3 experiments 1 micrometer of the fourth DKP preparation was shown to suppress PRL release slightly but significantly by 18%, (P less than 0.05). DKP did not enhance the dopamine-mediated inhibition of PRL release and it also did not reverse the TRH-mediated stimulation of PRL release by the pituitary gland in vitro. It was concluded that DKP (in micromolar concentrations) has a very weak PRL release-inhibiting action and is probably not a physiologically acting prolatin-inhibiting factor.

Animals↗

[Metastatic breast carcinoma in the pituitary gland (author's transl)].

Metastatic carcinoma was found in 9 pituitary glands (24%) of 37 patients undergoing transphenoidal hypophysectomy for diffuselly metastatic breast carcinoma. In all cases the preoperative neurological examination was negative, as were neuroradiological studies, including skull X-ray, tomograms of the sells turcicabrain scan, and angiography. Diabetes insipidus, however, was seen more frequently in patients with pituitary metastasis preoperatively (3 of 9) and postoperatively (8 of 9). Four of the nine patients with pituitary metastasis developed severe diabetes insipidus, which continued more than one month, while similar severe disease was seen in three of twenty-seven cases with no pathological evidence of pituitary metastasis. The prognosis in patients with pituitary metastasis was poor, with seven of the nine dying with an average survival of eighteen months. Pathological studies disclosed metastatic lesions in the anterior lobe (78%), posterior lobe (44%), and stalk (11%). The study emphasized that pituitary metastases, usually considered to be rare, occurred in 24% of patients with diffusely metastatic breast carcinoma. Such metastases correlate with the development of severe diabetes insipidus and with poor prognosis.

Adult↗

Correlated changes in the structure of the anterior pituitary gland, testes and interrenal tissue during sexual maturation of male lizards.

The anterior pituitary gland, testes and interrenal glands of a series of young males of the teiid Cnemidophorus l. lemniscatus (L.) have been studied by light microscopy in order to correlate the changes occurring during sexual maturation. In the testes of the smallest animals, spermatogenesis does not progress beyond primary spermatocytes and there is no differentiated interstitial tissue. In medium-sized animals, spermatids and some interstital cells appear, and in the largest lizards, spermatogenesis is completely established and Leydig cells abound. Simultaneously with the development of the testes, interrenal glands undergo great hypertrophy and hyperplasia, especially in the peripheral reactive zone. Starting in animals of intermediate size, the anterior hypophysis exhibits a considerable hypertrophy of two rostral cell types: the chromophobic corticotrophs and the acidophilic PAS-positive cells considered to be interstitiotrophs, These cells show large, vesicular nuclei and prominent nucleoli, signs of enhanced cellular activity. The hypertrophy begins in the dorso-rostral region of the gland close to the median eminence, at the site of entry of the portal vessels. This suggests a hypothalamic influence on the function of these pars distalis cells. The scattered basophilic gonadotrophs or folliculotrophs are scarce, small, and do not vary appreciably among the animals studied. The hyperactivity of corticotrophs may account for enlargement of the interrenal glands. Testicular development is apparently related to an increased activity of interstitiotrophs but to a stable level of activity in folliculotrophs.

Adrenal Glands↗