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PubMed2003

Best Practice No 172: pituitary gland pathology.

This article reviews published evidence on the diagnosis and classification of pituitary gland tumours and the relevance of histological and genetic features to prognosis. Much of the literature is devoted to the histological, ultrastructural, and immunocytochemical classification of pituitary adenomas (extensively supported by multicentre studies), with little consensus on the identification of prognostic features in adenomas, particularly in relation to invasion. There is a lack of correspondence between clinical and pathological criteria to identify and classify invasion, and a need to reassess the nomenclature and diagnostic criteria for invasive adenomas and carcinomas. Recent cytogenetic, genetic, and molecular biological studies have identified no consistent abnormalities in relation to pituitary tumour progression, although many genes are likely to be involved. In light of these uncertainties, an approach to the diagnosis and classification of pituitary adenomas is suggested, based on robust criteria from earlier studies and incorporating provisional data that require reassessment in large prospective studies with an adequate clinicopathological database.

Adenoma↗
PubMed1975

[A study on the regulatory mechanism of hypothalamo-hypophyseo-ovarian system in estrous cycles of rats: Changes in responsiveness of the anterior pituitary gland to synthetic LH-RH (author's transl)].

It is generally accepted that the sexual cycle in mammals is accomplished by the systematic coupling of components of the hypothalamo-hypophyseo-gonadal system. However, how these components are related to each other to develop the sexual cyclicity has not yet been clearly established. A gonadotropin releasing factor (GnRF), which has been extracted and purified from porcine hypothalamus and whose molecular structure was determined in 1971, has been synthesized in many laboratories. The synthetic GnRF, named LRF or LH-RH, has gonadotropin releasing activity for many species of mammals, including humans. The debut of the synthetic LRF has given us a pure material and a direct means of stimulating, relatively easily, the gonadotroph cells in the anterior pituitary glands. In the present study, variations in the gonadotropin releasing activity of the pituitary gland in relation to synthetic LRF was investigated throughout the sexual cycle of rats. The relationship between pituitary sensitivity and levels of steroid hormones in the blood is discussed.

Animals↗
PubMed1977

Purification and characterization of high-molecular-weight forms of adrenocorticotropic hormone of ovine pituitary glands.

A highly purified preparation of high-molecular-weight adrenocorticotropic hormone (ACTH) was prepared from ovine pituitary glands by dilute acetic acid extraction, oxycellulose fractionation. Sephadex gel filtration, and affinity chromatography on immobilized alphap(1-39)ACTH antibodies. Two ACTH peptides of molecular weights of 24 000 and 34 000 were detected by sodium dodecyl sulfate-acrylamide gel electrophoresis in this preparation. It appeared that the immobilized antibodies adsorbed two forms equally well and could not distinguish between them under the conditions used. These two ACTH peptides were found to be present in crude extracts of ovine pituitary glands, indicating that they were not artifacts produced by the purification procedure. The high-molecular-weight forms of ACTH were found to be susceptible to degradation by tissue enzymes. They could be easily destroyed during the extraction, if precautions were not taken. Moreover, they were poorly adsorbed by oxycellulose which had been used for the adsorption of ACTH activity from crude preparations by most investigators. These properties probably accounted for the fact that high-molecular-weight forms of ACTH remained undetected until very recently.

Adrenocorticotropic Hormone↗
PubMed1979

DNA synthesis in the pituitary gland of the rat: effect of sulpiride and clomiphene.

Sulpiride administration to rats releases prolactin and increases DNA replication in the anterior pituitary gland. Clomiphene prevents the stimulation of DNA synthesis produced by sulpiride, but does not affect prolactin release from the gland. These findings suggest that the intracellular prolactin content of the anterior pituitary gland plays a role in the regulation of DNA synthesis through a mechanism mediated by oestrogens.

Animals↗
PubMed1991

Methylation status of cKi-ras and MHC genes in rat pituitary glands during aging and tumorigenesis.

Methylation patterns of MHC (major histocompatibility complex) class I and vKi-ras (viral Kirsten-ras) homologous sequences in normal and adenomatous rat pituitary glands were studied as a function of age by Southern hybridization analysis using the isoschizomers Hpa II and Msp I. Both MHC class I and vKi-ras homologous sequences were found to be hypomethylated in a number of tumors, compared to normal pituitary gland tissue. However, despite reports indicating a general demethylation in mammalian tissues in relation to donor age, age-related methylation changes in this apparently methylation-unstable and cancer-prone organ were not observed.

Adenoma↗
PubMed2002

Estrogen and progesterone receptor content in the pituitary gland and uterus of progesterone-primed and gonadotropin releasing hormone-treated anestrous ewes.

The objective of this work was to investigate the effect of progesterone (P) and gonadotropin-releasing hormone (GnRH) treatment on estrogen receptor (ER) and P receptor (PR) concentrations in the pituitary gland and uterus of anestrous ewes. Ewes were either not treated (group C, n = 4); were treated with 0.33 g P-controlled internal drug release (P-CIDR) for 10 days (group P, n = 4), with GnRH, 6.7 ng i.v. injections every 2 h for 18 h followed by a 4 microg bolus administration of Receptal at 20 h (group GnRH, n = 4), or with a combination of the P and GnRH treatment (group P + GnRH, n = 3). Ewes were humanely killed either at the beginning of the experiment (group C), when the CIDR was removed (group P), or 24 h after the GnRH bolus treatment (groups GnRH and P + GnRH). Progesterone treatment increased serum P concentrations, indicating that the treatment was effective. All GnRH treated ewes had similar luteinizing hormone (LH) surges, which lasted 8 h. At slaughter, estradiol (E2) concentrations in the GnRH group were higher than in groups C, P, and P + GnRH. Treatment with GnRH increased more than 10-fold the content of ER and PR in the pituitary gland without altering steroid receptor concentrations in the uterus. When GnRH was combined with P the uterine receptor contents were higher than with P treatment alone. The treatment with P decreased ER and PR content in the uterus, but had no effect on the pituitary gland. The results show that regulation by P and GnRH of ER and PR content in anestrous ewes is tissue-specific.

Anestrus↗
PubMed1993

Immunohistochemical expression of PIT-1 protein in pituitary glands of human GRF transgenic mice: its relationship with hormonal expressions.

It has been suggested that pit-1 protein may play a role in the differentiation of the anterior pituitary cells. The present immunohistochemical studies were designed to elucidate the relationship between functional differentiation of pituitary adenoma and expression of pit-1 protein in human (h) GRF transgenic mice. Pituitaries from a 10 month old and a 6 month old transgenic mice were fixed in 4% paraformaldehyde and embedded in paraffin. The indirect immunoperoxidase method was performed using antibodies against hGRF, GH, PRL, ACTH, alpha subunit (SU), FSH beta SU, LH beta SU, TSH beta SU, and pit-1 protein. Immunohistochemical double staining was performed at light and electron microscopic levels. The pituitary glands of hGRF transgenic mice (both 10 month and 6 month old) demonstrated diffuse hyperplasia of GH positive cells with coexpression of hGRF within the same cells. There were also scattered cells which were positive for other hormones and hormone subunits in the hyperplastic pituitary. Three discrete nodules were found in the pituitary gland of a 10 month old hGRF transgenic mouse and were identified as adenomas. These adenomas were composed of enlarged round cells which were positive only for GH, hGRF, PRL and TSH beta SU. Pit-1 protein was intensely expressed in the nuclei of the adenoma cells. These results suggest the existence of an autocrine mechanism by hGRF in the formation of somato-lacto-thyrotroph adenoma via constitutive pit-1 expression.

Adenoma↗
PubMed1984

Bromocriptine-induced changes in the biochemistry, physiology, and histology of the intermediate lobe of the rat pituitary gland.

Treatment of rats with 2-Br-alpha-ergocryptine (bromocriptine; CB 154) elicits biochemical, physiological, and histological changes in the intermediate lobe (IL) of the rat pituitary gland, suggesting a decrease in activity in the IL. CB 154 treatment decreases 1) the capacity of the IL to synthesize proopiomelanocortin (POMC), 2) the content of mRNA directing the synthesis of POMC, and 3) the capacity of the IL to synthesize the peptides desacetyl alpha MSH, N,O-diacetyl alpha MSH, and alpha MSH. CB 154 treatment also causes a 40% loss of IL protein and an atrophy of the IL. CB 154 treatment has a biphasic effect upon the IL content of alpha MSH-like peptides; the drug first increases and then diminishes the content of these molecules. Control experiments using CB 154-treated IL tissue suggest that these effects of CB 154 are not a toxic effect of CB 154 on the IL. Spiroperidol reverses the effects of CB 154 on POMC synthesis and POMC mRNA content; by itself, spiroperidol increases the IL synthesis of POMC, the IL content of POMC mRNA, and the capacity of the IL to synthesize immunoreactive alpha MSH. Stalk section of rat pituitary gland also results in an increase in the capacity of the IL to synthesize POMC. These results suggest that a D-2 dopamine receptor mediates a tonic inhibition of the function of the IL.

Adrenocorticotropic Hormone↗
PubMed1977

Immature rat pituitary glands in vitro: age- and sex-related changes in luteinizing hormone releasing hormone-stimulated gonadotrophin release.

Pituitary glands from immature female and male rats aged between 5 and 30 days were incubated in vitro and the effect of LH releasing hormone (RH) on the release of LH and FSH was studied. Pituitary gonadotrophin contents were also measured. Gonadotrophin release showed changes with age as well as sex differences: after LH-RH stimulation the female pattern of release of LH and FSH (expressed per mg pituitary tissue) showed a peak at day 15; the male pattern of LH release was characterized by a steady increase with age, whereas FSH release stayed more or less constant from day 10 onwards. In both sexes the LH:FSH ratio increased with age, both in pituitary gonadotrophin content and in the mixture of gonadotrophins released. It is discussed, that the prepubertal development of pituitary gonadotrophic function might be determined on the one hand by rather autonomous growth processes (more or less similar in female and male hypophyses) and on the other hand by modulating influences of sex steroid hormones, which are different in female and male animals.

Age Factors↗
PubMed1983

Identification of endorphin acetyltransferase in rat brain and pituitary gland.

An enzyme which N-acetylates beta-endorphin has been identified and characterized in the rat brain and pituitary gland. The beta-endorphin acetyltransferase activity was localized almost exclusively in the intermediate lobe of the pituitary gland. beta-endorphin acetyltransferase activity was also present in the hypothalamus, a brain region which synthesizes beta-endorphin, but not the cerebellum, a region which does not synthesize beta-endorphin. The substrate specificity of beta-endorphin acetyltransferase appeared to be located in the NH2 terminus and midportions of the beta-endorphin sequence. The regional distribution and pharmacological specificity of beta-endorphin acetyltransferase indicate that it is a highly specialized regulatory enzyme. Because N-acetyl-beta-endorphin is nonanalgesic and does not bind to the opiate receptor (Smyth, D.G., Massey, D.E., Zakarian, S., and Finnie, M.D. (1979) Nature (Lond.) 279, 252-254), it appears that the physiological significance of beta-endorphin acetyltransferase is that it can modulate the activity of endorphin secreted from opiomelanotropinergic cells and neurons.

Acetyltransferases↗
PubMed1998

Pituitary gland and sella turcica in human trisomy 21 fetuses related to axial skeletal development.

The purpose of the present investigation was to study the sella turcica/pituitary gland region in trisomy 21 fetuses and to relate the findings in the region to the ossification pattern in the axial skeleton formed by the cranial base and spine. Material from 22 human fetuses with trisomy 21, CRL 80 mm to CRL 190 mm, corresponding to gestational ages from 14 to 21 weeks, was examined and compared with material from gestation-matched normal controls. After radiography, tissue blocks from the cranial base, including the pituitary gland, were examined and compared with those of normal fetuses. Four different types of sella turcica/ pituitary gland morphology were observed. Thirteen fetuses (Type I) were morphologically normal. Minor abnormalities occurred in the sella turcica and pituitary gland (adenopituitary gland tissue pharyngeally) in six fetuses (Types II and III). There was agreement between the histologically recorded deviations in the sella turcica and the radiographic observations of the basisphenoid bone. In three cases (Type IV) out of 22, more pronounced structural abnormalities occurred in the sella turcica, and radiographically the basisphenoid bone appeared cleft. All sella turcica changes observed in trisomy 21 were situated anteriorly in the base of the sella. In all cases the basilar part of the occipital bone was normal. Minor changes in the sella turcica region were mainly accompanied by cervical vertebral abnormalities, while the most severe abnormalities occurred in association with malformations in the lumbar vertebrae. There was no association between sella turcica malformations and the absence or presence of the nasal bone.

Bone and Bones↗
PubMed2000

[A case of metastatic tumor of the pituitary gland presenting as a subarachnoid hemorrhage].

We reported the case of a 55-year-old man with metastatic tumor of the pituitary gland who suffered from symptomatic pituitary apoplexy with subarachnoid hemorrhage. The patient, who had sigmoid colon carcinoma and left parietal metastatic brain tumor, developed severe headache and decrease of right visual acuity. CT showed a pituitary mass with subarachnoid hemorrhage. Transsphenoidal surgery was performed after replacement therapy with corticosteroids. Histological examination revealed metastasis of adenocarcinoma. Pituitary apoplexy is an unusual manifestation of metastatic pituitary tumor. The case of metastatic tumor of the pituitary gland presenting as subarachnoid hemorrhage such as this case is especial rare.

Adenocarcinoma↗
PubMed1997

Pit-1/growth hormone factor 1 splice variant expression in the rhesus monkey pituitary gland and the rhesus and human placenta.

We have examined the expression of Pit-1 messenger RNA (mRNA) splice variants in the nonhuman primate pituitary and in rhesus and human placenta. Full-length complementary DNAs (cDNAs) representing Pit-1 and the Pit-1 beta splice variants were cloned from a rhesus monkey pituitary cDNA library and were readily detectable by RT-PCR with rhesus pituitary gland RNA. The Pit-1T variant previously reported in mouse pituitary tumor cell lines was not detectable in normal rhesus pituitary tissue, although two novel splice variants were detected. A cDNA approximating the rat Pit-1 delta 4 variant was cloned but coded for a truncated and presumably nonfunctional protein. Only by using a nested RT-PCR approach were Pit-1 and Pit-1 beta variants consistently detectable in both human and rhesus placental tissue. The Pit-1 beta variant mRNA was not detectable in JEG-3 choriocarcinoma cells unless the cells were stimulated with 8-Br-cAMP. Immunoblot studies with nuclear extracts from primary rhesus syncytiotrophoblast cultures or JEG-3 choriocarcinoma cells indicated that although mRNA levels were very low, Pit-1 protein was detectable in differentiated cytotrophoblasts, and levels increased after treatment with 8-Br-cAMP. Two major species of Pit-1 protein were detected that corresponded to the two major bands in rat pituitary GH3 cell nuclear extracts. Low levels of slightly larger bands also were seen, which may represent Pit-1 beta protein or phosphorylated species. We conclude that Pit-1 splice variants expressed in the primate pituitary gland differ from those in the rodent gland and that the Pit-1 and Pit-1 beta mRNAs expressed in the placenta give rise to a pattern of protein expression similar to that seen in pituitary cells, which is inducible by treatment with 8-Br-cAMP.

Amino Acid Sequence↗
PubMed2005

Aromatase inhibition abolishes courtship behaviours in the ring dove (Streptopelia risoria) and reduces androgen and progesterone receptors in the hypothalamus and anterior pituitary gland.

The aim of this study was to determine in the ring dove, the effects of aromatase inhibition on the expression of aggressive courtship and nest-soliciting behaviours in relation to the distribution of cells containing immunoreactive androgen (AR) and progesterone (PR) receptor in the hypothalamus and pituitary gland. Isolated sexually experienced ring doves were transferred in opposite sex pairs to individual breeding cages, and then injected with the aromatase inhibitor, fadrozole (four males and four females), or saline vehicle (four males and four females) for 3 days at 12 hourly intervals. Saline-injected control males displayed aggressive courtship behaviours (bow-cooing and hop-charging) and nest-soliciting throughout the study, and control females displayed nest-soliciting. By day 3, fadrozole treatment resulted in the disappearance of all these behaviours and in a decrease or disappearance of AR and PR in the anterior pituitary gland, and in the nucleus preopticus paraventricularis magnocellularis (PPM), nucleus preopticus medialis (POM), nucleus hypothalami lateralis posterioris (PLH), and ventral, lateral and dorsal nucleus tuberalis in the hypothalamus (VTu, LTu, DTu). In the nucleus preopticus anterior (POA), fadrozole treatment decreased AR in both sexes and decreased PR in females but not in males. Cells containing co-localized nuclear AR and PR were found in all hypothalamic areas examined, and in the anterior pituitary gland. Fadrozole is suggested to reduce the local availability of estrogen required indirectly for the induction of AR, and except in cells containing PR in the male POA, for the direct induction of PR. It is suggested that aggressive courtship behaviour is terminated by "cross talk" between aromatase-independent PR and aromatase-dependent AR co-localized in neurons in the POA. Aromatase-independent PR may increase in the male POA in response to visual cues provided by a partner. Aromatase-dependent PR in the POM, and basal hypothalamus may play a role in the facilitatory effect of progesterone on estrogen-induced nest-orientated behaviours.

Animal Communication↗
PubMed1980

[The inhibitory effect of tolbutamide on both secretions of cortisol in the adrenal cortex and of prolactin in the pituitary gland (author's transl)].

It has been frequently postulated that insulin-induced hypoglycemia is widely employed clinically to assess the function of the hypothalamo-pituitary axis, being known to stimulate several pituitary trophic hormones such as HGH, ACTH, PRL (Prolactin), etc. Although tolbutamide produces hypoglycemia through the increase of endogenous insulin secretion, in the present study tolbutamide was used instead of insulin, and the effect of tolbutamide on the secretion of PRL from the pituitary gland and also on the secretion of cortisol from the adrenal cortex as well as HGH was studied, using 44 healthy normal subjects (male 35 and female 9, from 15 approximately 75 years of age). (1) PRL : One gram of tolbutamide injected into 5 normal subjects did not increase the serum concentration of PRL up to 120 minutes after the administration of the drug, while the concentration of PRL in the serum was increased clearly by the injection of insulin (0.1U/kg), with maximum PRL levels (approximately 50pg/ml) occurring at 60 minutes after the insulin administration. These results indicated strongly that tolbutamide inhibited the secretion of PRL from the pituitary gland. (2) Hypothalamo-Pituitary-Adrenal cortex : The same dose of tolbutamide as in the PRL experiment was also injected intravenously, and changes of serum cortisol levels were measured until 180 minutes after the injection of tolbutamide. It was found that levels of serum cortisol were clearly depressed within 30 minutes, and then the cortisol values started to increase up to 120 minutes after the administration of tolbutamide. The stimulatory effect of ACTH on the secretion of cortisol from the adrenal cortex was also strongly abolished by tolbutamide in the early phase as stated above. The data suggest that tolbutamide might have a direct inhibitory effect on the adrenal cortex as well as on pituitary PRL secretion.

Adolescent↗
PubMed1975

The responsiveness of the anterior pituitary gland to luteinizing hormone releasing factor in rats exposed to constant light.

The responsiveness of the anterior pituitary gland to synthetic luteinizing hormone releasing factor (LH-RF) was tested in rats exposed to constant light. At a dosage of 50 ng LH-RF/100 g body wt the mean maximal increments in plasma LH and FSH were similar to those at 10.00 h of pro-oestrus. The increments in the plasma gonadotrophins at dosages of 500 and 1000 ng LH-RF/100 g body wt did not differ significantly from those at 250 ng LH-RF/100 g body wt. These findings suggest that, in contrast to rats which exhibit regular oestrous cycles, the preovulatory (post-coital) release of LH in rats exposed to constant light may depend almost entirely on the release of a relatively large amount of LH-RF into hypophysial portal vessel blood. Whereas in pro-oestrous animals a relatively small fraction of the readily releasable pool of LH is released during the spontaneous preovulatory surge, in rats exposed to constant light most releasable LH appears to be discharged during the reflex preovulatory surge of this hormone. The concentrations of radioimmunoassayable FSH in blood samples withdrawn before the injection of LH-RF support the view that FSH secretion in the rat is increased by constant exposure to light.

Animals↗
PubMed1994

Insulin-like growth factor-I receptors in human brain and pituitary gland: an autoradiographic study.

Insulin-like growth factor (IGF)-I receptors were studied in adult human postmortem brain and pituitary gland using quantitative autoradiography with human recombinant [125I]IGF-I. The highest densities were found in the choroid plexus, pituitary gland--where IGF-I receptors were mainly concentrated in the anterior lobe, pineal gland, glomerular layer of the olfactory bulb, and the molecular layer of the cerebellar cortex. Moderate densities were present in cerebral cortex, caudate nucleus, putamen, accumbens, the CA1, CA2, CA3 fields and dentate gyrus of the hippocampus, the dentate nucleus of the cerebellum, amygdala, thalamus, pontine nuclei, and substantia nigra. All other brain areas, including white matter, contained low densities of IGF-I receptors. The finding that several well-defined brain structures are enriched with IGF-I receptors suggests a neurotrophic/survival or neuromodulatory role of insulin-like growth factors on specific neuronal systems. IGF-I receptors observed in the white matter may be associated with oligodendrocytes.

Adult↗