Cells Of Pars Distalis Research Articles

Therapeutic efficacy of adipose-derived mesenchymal stem cells after chronic fluoxetine treatment on pars distalis in adult male albino rats

BackgroundFluoxetine hydrochloride is one of the most commonly used antidepressants in the selective serotonin reuptake inhibitor class. The aim of work: The study was conducted to detect the effect of chronic fluoxetine treatment on pars distalis and the possible therapeutic effect of adipose-derived mesenchymal stem cells (ADSCs). Material and methodThirty healthy male adult albino rats were classified into four groups. Control group (Group I) included fifteen rats. Fluoxetine treated (Group II) included five rats that received 24 mg/kg/day of fluoxetine dissolved in 1.0 ml of tap water once a day for 30 days. Fluoxetine group treated with ADSCs (Group III) included five rats that received fluoxetine as group (II) for 30 days, then supplied once by ADSCs at a dose of 1 × 106 cells/rat in the tail vein suspended in 0.5 ml of phosphate-buffered saline (PBS). Recovery group (Group IV) included five rats that received fluoxetine as the group (II) then received no treatment till the end of the experiment. Samples from pars distalis were processed for light, electron microscopic examination, morphometrical and statistical analyses. ResultsIn the fluoxetine-treated group, there was a disruption in cellular architecture, size, shape, and staining characteristics of pars distalis cells. The administration of ADSCs significantly improved the microscopic appearance of cells, while the recovery group showed some histological changes similar to the fluoxetine group. ConclusionFluoxetine induced various deleterious changes in the pars distalis of albino rats. These changes were almost corrected by the ADSCs treatment.

Effects of crowding stress on the hypothalamo-pituitary-interrenal axis of the self-fertilizing fish, Kryptolebias marmoratus

We tested whether crowding stress affects the hypothalamo-pituitary-interrenal (HPI) axis of the self-fertilizing fish, Kryptolebias marmoratus, which is known to be aggressive in the laboratory conditions but sometimes found as a group from a single land crab burrow in the wild. The projection of corticotropin-releasing hormone (CRH) neurons to the adrenocorticotropic hormone (ACTH) cells in the pituitary was confirmed by dual-label immunohistochemistry; CRH-immunoreactive (ir) fibers originating from cell bodies located in the lateral tuberal nucleus (NLT) of the hypothalamus were observed to project to ACTH-ir cells in the rostral pars distalis of the pituitary. Then, fish were reared solitary or in pairs for 14 days, and the number of CRH-ir cell bodies in the NLT of the hypothalamus and cortisol levels in the body without head region were compared. The number of CRH-ir cell bodies and cortisol levels were significantly higher in paired fish. These results indicate that crowding stress affects the HPI axis in K. marmoratus which thrive in small burrows with limited water volume.

Does repeated gold-nanoparticles administration affect pars distalis hormonal and folliculo-stellate cells in adult male albino rats?

Worldwide, nanoparticles especially gold-nanoparticles (Au-NPs) are widely used in medicine, cancer treatment and cosmetic industry. They are easily conjugated with different biomedical and biological agents and effortlessly absorbed with few side effects. The pars distalis of the pituitary gland is considered as the maestro of the endocrine peripheral glands since it secrets trophic hormones that controls their functions. 5-10% of the non-granular pars distalis cells are folliculo-stellate cells (FSCs) that support the granular cells' functions. The aim of the study was to explore the histological and the biochemical effects of repeated exposure to Au-NPs on the pars distalis in adult male albino rats with highlighting the impact on FSCs. Thirty-six adult male albino rats were divided equally into control group and Au-NPs group (received 40 μg/kg/day of 11 ± 2 nm spherical Au-NPs orally for 2 weeks). Then, rats were euthanized and deposition of Au-NPs in pars distalis was investigated. Biochemical investigations and histological studies including hematoxylin and eosin staining, periodic acid Schiff's reaction, immunohistochemistry (IHC) for S-100, connexin 43 (Cx43) and Cytochrome-C (Cyt-C) as well as electron-microscopic and morphometric studies were carried out. The Au-NPs group demonstrated structural disorganization in the pars distalis, inflammation, congestion and increased extracellular PAS-positive colloid deposition due to the accumulation of Au-NPs. A significant increase in the immunoreactivity of S-100, Cx43 and Cyt-c, along with a significant increase in TNF-a, MDA, and bFGF content in the pituitary homogenates, was noted as compared to the control group. Ultrastructurally, degenerative changes were observed in the secretory cells. FSCs showed proliferation and increased phagocytic activity. Repetitive exposure of adult male albino rats to Au-NPs prompted the accumulation of these nanoparticles in the pars distalis that was accompanied by cellular degeneration and dysfunction of the secretory cell and proliferation of FSCs. Thus, monitoring of the pars distalis hormonal levels might be useful for early detection of some hazardous effects possibly associated with the use of gold-nanoparticles.

Transcriptional regulation of prolactin in a euryhaline teleost: Characterisation of gene promoters through in silico and transcriptome analyses.

The sensitivity of prolactin (Prl) cells of the Mozambique tilapia (Oreochromis mossambicus) pituitary to variations in extracellular osmolality enables investigations into how osmoreception underlies patterns of hormone secretion. Through the actions of their main secretory products, Prl cells play a key role in supporting hydromineral balance of fishes by controlling the major osmoregulatory organs (ie, gill, intestine and kidney). The release of Prl from isolated cells of the rostral pars distalis (RPD) occurs in direct response to physiologically relevant reductions in extracellular osmolality. Although the particular signal transduction pathways that link osmotic conditions to Prl secretion have been identified, the processes that underlie hyposmotic induction of prl gene expression remain unknown. In this short review, we describe two distinct tilapia gene loci that encode Prl177 and Prl188 . From our in silico analyses of prl177 and prl188 promoter regions (approximately 1000bp) and a transcriptome analysis of RPDs from fresh water (FW)- and seawater (SW)-acclimated tilapia, we propose a working model for how multiple transcription factors link osmoreceptive processes with adaptive patterns of prl177 and prl188 gene expression. We confirmed via RNA-sequencing and a quantitative polymerase chain reaction that multiple transcription factors emerging as predicted regulators of prl gene expression are expressed in the RPD of tilapia. In particular, gene transcripts encoding pou1f1, stat3, creb3l1, pbxip1a and stat1a were highly expressed; creb3l1, pbxip1a and stat1a were elevated in fish acclimated to SW vs FW. Combined, our in silico and transcriptome analyses set a path for resolving how adaptive patterns of Prl secretion are achieved via the integration of osmoreceptive processes with the control of prl gene transcription.

A Biochemichal and Ultrastructural Study on the Effect of Toluene on the Pars Distalis of Anterior Pituitary Glands of Adult Male Albino Rats

Background: Toluene is an environmental chemical pollutant and widely used as organic solvent and in production of many industrial products. It has systemic toxic effects on many organs as liver, kidney and the central nervous system and cause immune dysfunction. It can affect nerve myelination and cross the blood-brain barrier. Little is known about the exact effect of toluene exposure on the cells of anterior pituitary and no adequate studies were found about the effect of toluene on the morphological and histological structure of the pituitary cells.Aim: To assess the ultra structural of the pars distalis after toluene exposure. And to correlate any biochemical changes with the histological alteration as a trial to know the possible mechanism behind these changes.Materials and Methods: 20 adult male albino rats were divided into control group consisted of 10 rats and toluene exposed group 10 rats were exposed once a day to vapors of toluene (1000 ppm) for 15 minutes for 45 days. Blood samples were taken from the heart chambers of for assessment of the thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), luteinizing hormone (LH), adrencorticotrophic hormone (ACTH), growth hormone (GH) and prolactin. The anterior lobes of pituitary glands were immediately dissected out. Each specimen was separated into two parts; one processed and stained with hematoxylin & eosin and the other part was examined by electron microscope.Results: Biochemical: in the toluene-exposed group there was significant reduction in plasma level of GH, TSH, FSH and LH hormones and non-significant reduction in ACTH prolactin.Microscopic: the exposed group cells show complete loss of normal architecture in many areas and had vacuolated cytoplasm, shrunken asymmetrical nucleus with more thickened chromatin and few secretory granules.Conclusion: The toluene exposure induced morphological changes in most of cells of pars distalis and their secreted hormones

Chemokine CXCL14-like immunoreactivity in the αMSH-producing cells and PRL-producing cells of the flat-tailed house gecko pituitary.

The distribution pattern of chemokine CXCL14-immunoreactive cells was examined by immunohistochemistry in the pituitary of the gecko Hemidactylus platyurus. Immunoreactive cells were observed in the pars intermedia and pars distalis of the pituitary, but not in the pars nervosa. All α-melanocyte-stimulating hormone (αMSH)-producing cells were immunoreactive for CXCL14 in the pars intermedia. The CXCL14-immunoreactive cells corresponded to prolactin (PRL)-producing cells but not to other adenohypophyseal-hormone-producing cells in the pars distalis. CXCL14 secreted from αMSH-producing cells and PRL-producing cells may regulate insulin release from β cells in the pancreatic islets as well as glucose uptake in the muscle cells together with αMSH and/or PRL. In addition, secreted CXCL14 with αMSH and/or PRL may act as a bioactive factor regulating hormone release in the adenohypophyseal cells of the reptilian pars distalis.

Influence of endomorphins along the pituitary-ovary axis in the Mozambique Tilapia Oreochromis mossambicus.

Endomorphins (EM-1 and EM-2) are the tetrapeptides involved in pain and neuroendocrine responses with a high affinity for μ-opioid receptors in vertebrates. However, their role in fish reproduction is not clear. The aim of this study was to investigate the influence of EM-1 and EM-2 on the pituitary-ovary axis in the Mozambique tilapia Oreochromis mossambicus. The experimental set-up consisted of four groups, namely, initial controls, controls, EM-1- and EM-2-treated groups (n = 10 in each group consisting of two replicates). Although the number of stage IV (vitellogenic) follicles was significantly lower (P < 0.05) in controls compared to initial controls, the stage V (preovulatory) follicles were present in controls in contrast to their absence in initial controls. Treatment of 40 μg EM-1/0.1 ml saline/fish/day for 22 days resulted in significant increase (P < 0.05) in the number of stage I follicles compared to controls. While similar treatment of EM-2 did not significantly alter the number of stage I follicles compared to controls, the number of stage II follicles was significantly lower (P < 0.05) in this group compared to those of controls and EM-1 treated fish. The number of stage III and IV follicles did not significantly differ among controls, EM-1- and EM-2-treated groups. However, a significant reduction (P < 0.05) in the mean number of stage V follicles was observed in EM-1- and EM-2-treated fish compared to controls. These changes were concomitant with significant reduction (P < 0.05) in the intensity and the percent area of immunoreactivity of luteinizing hormone (LH) secreting cells in the proximal pars distalis (PPD) of the pituitary gland and significantly higher (P < 0.05) percent occurrence of follicular atresia in EM-1- and EM-2-treated fish compared to those of controls. Taken together, these results suggest an inhibitory effect for endomorphins along the pituitary-ovary axis, for the first time in fish.

Exposure to hypoxia inhibits pituitary-testicular activity in the fish Oreochromis mossambicus

Fishes are exposed to natural hypoxic conditions during aquacultural practices. Although negative effects of hypoxia are documented on fish reproduction, the mechanism of hypoxia-induced alteration in spermatogenic process is not well understood in continuously breeding fishes. The aim of this investigation was to determine the influence of hypoxia on pituitary-testicular activity in the tilapia Oreochromis mossambicus, a cichlid fish that breeds throughout the year. The fish were exposed to moderate hypoxia (MH, Dissolved oxygen (DO) level, 3.24 ± 0.22 mg/L) and severe hypoxia (SH, DO level, 1.64 ± 0.38 mg/L) for 21 days. No significant differences were noticed in the mean numbers of spermatogonia (Sg), primary spermatocytes (Ps), secondary spermatocytes (Ss), early spermatids (Est) and late spermatids (Lst) between controls and fish subjected to MH, whereas the numbers of these cells were significantly lower in fish exposed to SH. Furthermore, weakly immunoreactive luteinizing hormone (LH) secreting cells in the proximal pars distalis (PPD) of the pituitary gland were concomitant with significant reduction in mean serum levels of LH and testosterone as well as androgen receptor immunoreactivity in the Sertoli cells in the testis of fish exposed to SH compared to other groups. On the other hand, the serum cortisol levels were significantly higher in fish exposed to SH compared with other experimental groups. Taken together, these results indicate that the tilapia is able to withstand the moderate hypoxic condition, whereas exposure to severe hypoxic condition suppresses the process of spermatogenesis through the inhibition of LH secretion, which in turn might suppress the testicular steroidogenesis and androgen receptor expression in the Sertoli cells. The results also suggest a possibility that this inhibition might be mediated through the activation of stress-axis in O. mossambicus.

Tetrodotoxin functions as a stress relieving substance in juvenile tiger puffer Takifugu rubripes

We tested whether tetrodotoxin (TTX) functions as a stress relieving substance in puffer fish. We orally administered TTX to the juveniles of hatchery-reared non-toxic tiger puffer Takifugu rubripes and measured the effects of TTX on brain corticotropin-releasing hormone (CRH) mRNA expression and plasma cortisol levels in comparison with effects in non-toxic juveniles. Firstly, the reciprocal connections of CRH and adrenocorticotropic hormone (ACTH) were confirmed by dual-label immunohistochemistry. CRH-immunoreactive (ir) cell bodies were detected in the hypothalamus and CRH-ir fibers were observed to project to ACTH-ir cells in the rostral pars distalis of the pituitary. Next, a TTX-containing diet (2.35 mouse units (517 ng)/g diet) or a non-toxic diet were fed to the fish for 28 days under a recirculating system. Standard length and body weight became significantly larger in the TTX-treated group. The degree of loss of the caudal fin, which is an indicator of the degree of agonistic interactions, where high values show a higher loss of caudal fin of a fish due to nipping by other individuals, was significantly lower in the TTX-treated group. Relative CRH mRNA expression levels in the brain and cortisol levels in the plasma were significantly lower in the TTX-treated group. These results indicate that TTX functions as a stress relieving substance by affecting the CRH-ACTH-cortisol axis and reducing agonistic interactions in tiger puffer juveniles.

Localization, distribution and expression of growth hormone in the brain of Asian Catfish, Clarias batrachus.

Intense immunoreactivity was observed in several neurons of the nucleus preopticus (NPO) located in the preoptic area (POA), in addition to several GH cells in the proximal pars distalis (PPD) of the pituitary gland of Clarias batrachus. The immunoreactive cells were located in the paraventricular as well as supraoptic subdivisions of the NPO. GH immunoreactive fibers projecting from the neurons were traced caudally to the pituitary gland via the conspicuous preoptico-hypophysial tract (PHT) in the ventral tuberal area to the neurohypophysis of the pituitary. Apart from these immunoreactive fibers in the preoptico-hypophysial tract, some fine caliber fiber probably arising from the neurons located dorsally in the NPO also showed GH immunoreactivity, and these fibers constituted an independent tract. Bilaterally, it extended caudally through the dorsal hypothalamus almost as far as the saccus vasculosus where it curved sharply to descend into the caudal tuberal region and finally entered into the pituitary gland. The fibers of this tract were mainly distributed in the rostral pars distalis (RPD). This tract is quite distinct from the preoptico-hypophysial tract and herein called as the accessory preoptico-hypophysial tract (APHT). Expression of GH mRNA in the NPO was found 65-fold more than that of the control region, rostral cerebellum. These results altogether suggest that GH secreted by NPO neurons might serve as a neuro-modulatory role in the brain of C. batrachus. Transportation of GH to the pituitary via two independent tracts may represent the duality of neuroendocrine function. The present study underscores the possibility that GH in the brain of vertebrates may be a phylogenetically conserved phenomenon and provide clues to our understanding of the evolutionary course taken by the hormone.

Influence of cortisol along the pituitary-ovary axis in the cichlid fish Oreochromis mossambicus

Cortisol is the principal glucocorticoid released due to various forms of environmental as well as aquacultural stressors in fish. The aim of the present investigation was to determine cortisol-induced alterations along the luteinizing hormone (LH)-secreting cells–ovary axis in the tilapia Oreochromis mossambicus. Administration of cortisol to stripped O. mossambicus for a period of 22 days during the ovarian cycle caused significantly higher number of follicles with chromatin nucleoli (stage I) compared to those of initial controls and controls. Whereas the number of follicles at perinucleolar (stage II) and vitellogenic (stage IV) stages did not differ significantly between controls and cortisol-treated fish, the number of follicles at cortical alveolar stage (stage III) was significantly lower in cortisol-treated fish than in controls. While the stage V follicles (maturation stage) were absent in initial controls, their presence in controls was concomitant with intensely labelled LH-secreting cells in the proximal pars distalis (PPD) region of the pituitary gland during prespawning phase. However, cortisol-treatment resulted in complete absence of stage V follicles associated with weakly immunoreactive LH-content in the PPD region of the pituitary gland during prespawning phase. These results suggest that chronic cortisol- treatment causes suppression of LH-secreting cells activity and blocks progression of vitellogenic follicular development process in O. mossambicus.

Histological changes in pituitary-testes axis in rats exposed to cadmium chloride: Protective role of Eruca sativa seeds

The present study was carried out to investigate the protective effect of Eruca sativa seeds against changes of pituitary and testes in cadmium treated rats. Forty adult male albino rats were used and divided into 4 equal groups and treated for 8 weeks as follow: The first group was given distilled water and used as a control group. The second group (G1) was administered tap water containing 30 ppm/ L of cadmium chloride. Animals in third group (G2) received tap water containing Cadmium chloride as in G1 plus 250 mg/Kg B.W ethanolic extract of Eruca sativa seeds, while rats in fourth group (G3) administered 250 mg/Kg B.W of ethanolic extract of Eruca sativa seeds only. After 8 weeks of experiment the animals were anesthetized, the pituitary and testes were excised for histological studies. Results showed that cadmium chloride intake caused severe alterations in the pituitary gland manifested by a marked apoptotic cells of pars distalis, accompanied with marked necrosis leading to left large multiple spaces in their parenchyma. Whereas testes revealed shrinkage, irregular arrangement of seminiferous tubules and increase intertubular spaces. A considerable changes was also found in the seminiferous tubules with loss most of their epithelial layer and filled with cellular debris, incomplete spermatogenesis, congested blood vessels and few Leydig's cells. Administration of Eruca sativa extract reduce the deleterious effects of cadmium chloride on pituitary gland as well as more or less complete spermatogenesis process with thickness of interstitial tissue in most of seminiferous tubules. It could be suggested that the antioxidant properties of Eruca sativa extract protects the deleterious histological damage induced by cadmium chloride in adult rats.

Gonadotropin subunits of the characiform Astyanax altiparanae: Molecular characterization, spatiotemporal expression and their possible role on female reproductive dysfunction in captivity

To better understand the endocrine control of reproduction in Characiformes and the reproductive dysfunctions that commonly occur in migratory fish of this order when kept in captivity, we chose Astyanax altiparanae, which has asynchronous ovarian development and multiple spawning events, as model species. From A. altiparanae pituitary total RNA, we cloned the full-length cDNAs coding for the follicle-stimulating hormone β subunit (fshb), the luteinizing hormone β subunit (lhb), and the common gonadotropin α subunit (gpha). All three sequences showed the highest degree of amino acid identity with other homologous sequences from Siluriformes and Cypriniformes. Real-time, quantitative PCR analysis showed that gpha, fshb and lhb mRNAs were restricted to the pituitary gland. In situ hybridization and immunofluorescence, using specific-developed and characterized polyclonal antibodies, revealed that both gonadotropin β subunits mRNAs/proteins are expressed by distinct populations of gonadotropic cells in the proximal pars distalis. No marked variations for lhb transcripts levels were detected during the reproductive cycle, and 17α,20β-dihydroxy-4-pregnen-3-one plasma levels were also constant, suggesting that the reproductive dysfunction seen in A. altiparanae females in captivity are probably due to a lack of increase of Lh synthesis during spawning season. In contrast, fshb transcripts changed significantly during the reproductive cycle, although estradiol-17β (E2) levels remained constant during the experiment, possibly due to a differential regulation of E2 synthesis. Taken together, these data demonstrate the putative involvement of gonadotropin signaling on the impairment of the reproductive function in a migratory species when kept in captivity. Future experimental studies must be carried to clarify this hypothesis. All these data open the possibility for further basic and applied studies related to reproduction in this fish model.

Neuroanatomical evidence for the involvement of β-endorphin during reproductive stress response in the fish Oreochromis mossambicus

Although neuroendocrine regulation of stress response involving hypothalamo-pituitary-adrenal axis is well established in mammals, the mechanism of functioning of endocrine-stress axis is not completely elucidated in fish. Our previous studies suggested a possible role for the opioidergic mediation of reproductive stress response in fish. In the present investigation, by immunocytochemical approach, we studied the distribution of β-endorphin (β-EP) secreting neurons in the brain of the tilapia Oreochromis mossambicus exposed to aquacultural stressors. Intensely stained β-EP immunoreactive neurons were encountered in the nucleus lateralis tuberis (NLT) region during previtellogenic and vitellogenic phases in both controls and in fish exposed to aquacultural stressors. Furthermore, at the end of the prespawning phase in controls, weak staining in β-EP neurons was accompanied by intensely stained luteinizing hormone (LH) immunoreactive cells in the proximal pars distalis (PPD) of the pituitary gland and a significantly higher gonadosomatic and hepatosomatic indices, suggesting the attenuation of inhibitory effect of β-EP on reproductive axis prior to spawning. However, in fish exposed to stressors, several darkly stained β-EP immunoreactive cells with dense fibre projections towards the hypothalamo-hypophysial tract were concomitant with weakly immunoreactive LH content in the PPD of the pituitary gland and a significantly lower gonadosomatic and hepatosomatic indices compared to those of controls. These results suggest that stress-induced activation of β-EP secreting neurons in the NLT region might lead to the inhibition of LH secreting cells-ovary axis in fish.

Cloning of corticotropin-releasing hormone (CRH) precursor cDNA and immunohistochemical detection of CRH peptide in the brain of the Japanese eel, paying special attention to gonadotropin-releasing hormone

The stress-related corticotropin-releasing hormone (CRH) was first identified by isolation of its cDNA from the brain of the Japanese eel Anguilla japonica. CRH cDNA encodes a signal peptide, a cryptic peptide and CRH (41 amino acids). The sequence homology to mammalian CRH is high. Next, the distribution of CRH-immunoreactive (ir) cell bodies and fibers in the brain and pituitary were examined by immunohistochemistry. CRH-ir cell bodies were detected in several brain regions, e.g., nucleus preopticus pars magnocellularis, nucleus preopticus pars gigantocellularis and formatio reticularis superius. In the brain, CRH-ir fibers were distributed not only in the hypothalamus but also in various regions. Some CRH-ir fibers projected to adrenocorticotropic hormone (ACTH) cells in the rostral pars distalis of the pituitary and also the α-melanocyte-stimulating hormone (α-MSH) cells in the pars intermedia of the pituitary. Finally, the neuroanatomical relationship between the CRH neurons and gonadotropin-releasing hormone (GnRH) neurons was examined by dual-label immunohistochemistry. CRH-ir fibers were found to be in close contact with GnRH-ir cell bodies in the hypothalamus and in the midbrain tegmentum and GnRH-ir fibers were in close contact with CRH-ir cell bodies in the nucleus preopticus pars magnocellularis. These results suggest that CRH has some physiological functions other than the stimulation of ACTH and α-MSH secretion and that reciprocal connections may exist between the CRH neurons and GnRH neurons in the brain of the Japanese eel.

Kisspeptin-1 directly stimulates LH and GH secretion from goldfish pituitary cells in a Ca2+-dependent manner

It has been established that kisspeptin regulates reproduction via stimulation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion, which then induces pituitary luteinizing hormone (LH) release. Kisspeptin also directly stimulates pituitary hormone release in some mammals. However, in goldfish, whether kisspeptin directly affects pituitary hormone release is controversial. In this study, synthetic goldfish kisspeptin-1(1–10) (gKiss1) enhances LH and growth hormone (GH) release from primary cultures of goldfish pituitary cells in column perifusion. gKiss1 stimulation of LH and GH secretion were still manifested in the presence of the two native goldfish GnRHs, salmon (s)GnRH (goldfish GnRH-3) and chicken (c)GnRH-II (goldfish GnRH-2), but were attenuated by two voltage-sensitive calcium channel blockers, verapamil and nifedipine. gKiss-induced increases in intracellular Ca2+ in Fura-2AM pre-loaded goldfish pars distalis cells were also inhibited by nifedipine. These results indicate that, in goldfish, (1) direct gKiss1 actions on pituitary LH and GH secretion exist, (2) these actions are independent of GnRH and (3) they involve Ca2+ signalling.

Characterization of Xenobiotic-Induced Hepatocellular Enzyme Induction in Rats

During routine safety evaluation of RO2910, a non-nucleoside reverse transcriptase inhibitor for HIV infection, histopathology findings concurrent with robust hepatocellular induction occurred in multiple organs, including a unique, albeit related, finding in the pituitary gland. For fourteen days, male and female rats were administered, by oral gavage vehicle, 100, 300, or 1000 mg/kg/day of RO2910. Treated groups had elevated serum thyroid-stimulating hormone and decreased total thyroxine, and hypertrophy in the liver, thyroid gland, and pituitary pars distalis. These were considered consequences of hepatocellular induction and often were dose dependent and more pronounced in males than in females. Hepatocellular centrilobular hypertrophy corresponded with increased expression of cytochrome P450s 2B1/2, 3A1, and 3A2 and UGT 2B1. Bilateral thyroid follicular cell hypertrophy occurred concurrent to increased mitotic activity and sometimes colloid depletion, which were attributed to changes in thyroid hormone levels. Males had hypertrophy of thyroid-stimulating hormone-producing cells (thyrotrophs) in the pituitary pars distalis. All findings were consistent with the well-established adaptive physiologic response of rodents to xenobiotic-induced hepatocellular microsomal enzyme induction. Although the effects on the pituitary gland following hepatic enzyme induction-mediated hypothyroidism have not been reported previously, other models of stress and thyroid depletion leading to pituitary stimulation support such a shared pathogenesis.

Divergence of duplicate POMC genes in gilthead sea bream Sparus auratus

Proopiomelanocorticotrophin (POMC) in vertebrates is produced in the pituitary gland and undergoes post-translational processing to give rise to a range of biologically active peptides. Teleosts possess 2–3 different POMC transcripts which have been proposed to have originated from a whole or partial genome duplication. In the present study 2 transcripts of gilthead sea bream POMC (sbPOMC-α1 and α2) were cloned and characterised. sbPOMC-α1 is expressed principally in the melanotroph cells of the pars intermedia (PI) and sbPOMC-α2 is expressed in the corticotroph cells of the rostral pars distalis and probably also in the PI. The 2 sbPOMC transcripts have a differential tissue distribution in extra-pituitary sites. An appraisal of POMC evolution indicates sbPOMCs belong to one of the two main clades that exist in teleosts and that overall a non conservative process of gene loss occurred in this infraclass.

Effect of the photoperiod and administration of melatonin on folliculostellate cells of the pituitary pars distalis of adult male viscacha ( Lagostomus maximus maximus)

Numerous reports have shown the effect of photoperiod and melatonin administration on the different hormone secreting cell types in the pituitary pars distalis. The viscacha ( Lagostomus maximus maximus) is a rodent with photoperiod-dependent seasonal reproduction. The aim of this study was to examine the effect of photoperiod seasonal variations and melatonin administration on the folliculostellate cells in pituitary pars distalis of viscacha. Immunohistochemistry and image analysis were used to measure the percentage of S-100-positive area (total, cellular and colloidal) and the number of folliculostellate cells. The S-100 protein was immunolocalized at intracellular (folliculostellate cells) and extracellular (follicular colloid) levels. The morphometric parameters analyzed exhibited seasonal variations with highest values in the summer (long photoperiod) and lowest values in the winter (short photoperiod). The administration of melatonin caused a significant decrease of immunostaining. Results suggest that the natural photoperiod might be the most important environmental signal causing the decrease in folliculostellate cells immunostaining observed in the winter. These findings agree with seasonal changes previously reported in endocrine cells and suggest that folliculostellate cells may be involved in the paracrine regulation of the secretory activity of pituitary pars distalis through S-100 protein production.

Folliculostellate cells in pituitary pars distalis of male viscacha: immunohistochemical, morphometric and ultrastructural study.

Folliculostellate cells (FSC) have been reported in pituitary of several mammalian species. FSC morphology and secreted substances have been instrumental to the understanding of their function. The purpose of this work was to perform an immunohistochemical, morphometric and ultrastructural study of the pituitary pars distalis FSC in adult male viscacha and to analyze their relation with hormone secreting cells. Immunohistochemistry and image analysis were carried out in different sectors of the gland, from the middle (sector 1) to the glandular periphery (sector 5). Transmission electron microscopy with lanthanum as electrodense tracer was used. FSC formed follicles with PAS-positive colloid inside. They expressed S-100 protein mainly in both nucleus and cytoplasm. FSC were stellate-like in shape and exhibited short cytoplasmic processes that contacted with blood vessels and endocrine cells. In addition, some follicular colloids were immunostained with anti-S-100 protein. A few FSC were immunostained with anti-glial fibrillary acidic protein (GFAP) and anti-vimentin. The morphometric parameters analyzed (percentages of S-100-positive total, cellular and colloidal areas) increased from sector 1 to sector 3 and then decreased to sector 5. Hormone secreting cells, mainly lactotrophs, gonadotrophs and corticotrophs were associated with FSC and follicles. The ultrastructural study demonstrated that FSC developed junctional complexes and desmosomes between their lateral membranes. Lanthanum freely penetrated the spaces between granulated cells and FSC, but did not penetrate into the follicular lumen. In conclusion: 1) the differential expression of S-100 protein, GFAP and vimentin may indicate different physiological stages of FSC; 2) the expression of these proteins suggests a neuroectodermic origin of these cells; 3) FSC spatial distribution, association with endocrine cells, and the generation of an intercellular communication network suggest that FSC are involved in the pituitary pars distalis paracrine regulation of the viscacha.