Triiodothyronine Rapidly Alters the TSH Content and the Secretory Granules Distribution in Male Rat Thyrotrophs by a Cytoskeleton Rearrangement-Independent Mechanism

Rapid actions of T3 on TSH synthesis in posttranscriptional steps, such as polyadenylation and translation rate, have already been described. The focus of this paper was to characterize rapid actions of T3 on TSH secretion and the involvement of actin and microtubule cytoskeleton in this process. For that, sham-operated (SO) and thyroidectomized (Tx) rats were subjected to acute or chronic treatment with T3. We observed a disarrangement in microtubule and actin cytoskeletons and an increase in Tshb mRNA levels in Tx rats, whereas the total TSH protein content was reduced in the pituitary gland as a whole, but increased in the secretory granules close to the plasma membrane of thyrotrophs, as well as in the extracellular space. The acute T3 dose promoted a rapid increase and redistribution of TSH secretory granules throughout the cytoplasm, as well as a rearrangement in actin and microtubule cytoskeletons. The T3 chronic treatment outcome reinforces the acute effects observed and, additionally, evinces an increase in the α-tubulin content and a rearrangement in microtubule cytoskeleton. Thus, T3 is able to rapidly suppress TSH secretion and, in parallel, to promote a rearrangement in actin and microtubules assembly throughout the pituitary gland, effects that seem to be independent from each other.

Download Full-text

Inhibition of the Type 2 Iodothyronine Deiodinase Underlies the Elevated Plasma TSH Associated with Amiodarone Treatment

Endocrinology ◽

10.1210/en.2010-0553 ◽

2010 ◽

Vol 151 (12) ◽

pp. 5961-5970 ◽

Cited By ~ 50

Author(s):

Matthew L. Rosene ◽

Gábor Wittmann ◽

Rafael Arrojo e Drigo ◽

Praful S. Singru ◽

Ronald M. Lechan ◽

...

Keyword(s):

Pituitary Gland ◽

Critical Role ◽

Feedback Mechanism ◽

Mrna Levels ◽

Iodothyronine Deiodinase ◽

Hek 293 ◽

Tsh Secretion ◽

Dependent Inhibition ◽

Noncompetitive Inhibitors

The widely prescribed cardiac antiarrhythmic drug amiodarone (AMIO) and its main metabolite, desethylamiodarone (DEA), have multiple side effects on thyroid economy, including an elevation in serum TSH levels. To study the AMIO effect on TSH, mice with targeted disruption of the type 2 deiodinase gene (D2KO) were treated with 80 mg/kg AMIO for 4 wk. Only wild-type (WT) mice controls developed the expected approximate twofold rise in plasma TSH, illustrating a critical role for D2 in this mechanism. A disruption in the D2 pathway caused by AMIO could interfere with the transduction of the T4 signal, generating less T3 and softening the TSH feedback mechanism. When added directly to sonicates of HEK-293 cells transiently expressing D2, both AMIO and DEA behaved as noncompetitive inhibitors of D2 [IC(50) of >100 μm and ∼5 μm, respectively]. Accordingly, D2 activity was significantly decreased in the median eminence and anterior pituitary sonicates of AMIO-treated mice. However, the underlying effect on TSH is likely to be at the pituitary gland given that in AMIO-treated mice the paraventricular TRH mRNA levels (which are negatively regulated by D2-generated T3) were decreased. In contrast, AMIO and DEA both exhibited dose-dependent inhibition of D2 activity and elevation of TSH secretion in intact TαT1 cells, a pituitary thyrotroph cell line used to model the TSH feedback mechanism. In conclusion, AMIO and DEA are noncompetitive inhibitors of D2, with DEA being much more potent, and this inhibition at the level of the pituitary gland contributes to the rise in TSH seen in patients taking AMIO.

Download Full-text

Evidence for direct action of calcitonin in the rat pituitary gland

Acta Endocrinologica ◽

10.1530/acta.0.1200682 ◽

1989 ◽

Vol 120 (5) ◽

pp. 682-688 ◽

Cited By ~ 5

Author(s):

G. Morel ◽

J.-G. Chabot ◽

A. Enjalbert ◽

M. Priam ◽

P. M. Dubois

Keyword(s):

Pituitary Gland ◽

Anterior Pituitary ◽

Direct Action ◽

Secretory Granules ◽

In Vitro Study ◽

Male Rat ◽

Pituitary Cells ◽

Cytoplasmic Matrix ◽

Rat Pituitary

Abstract. Classic concepts of calcitonin (CT) function have focused on the effects of CT on calcium homeostasis. More recently CT actions on brain and pituitary have been investigated. In order to evaluate the effects of CT on the anterior pituitary gland we studied the action(s) of CT in vitro and visualized endogenous CT in adult male rat pituitary gland by immunocytochemistry on ultrathin sections obtained by cryoultramicomy. In vitro study using dispersed anterior pituitary cells indicated that CT stimulated the secretion of PRL, whereas the secretion of GH, TSH and LH was not affected. CT-like immunoreactivity was observed in lactotropes only. The other pituitary cell types were not immunoreactive. In lactotropes, immunostaining was observed in the cytoplasm and in the nucleus. In the cytoplasm, CT-like immunoreactivity was visuzalized in the cytoplasmic matrix and in the secretory granules. In the nucleus, immunostaining was distributed primarly in the euchromatin, in the vincinity of heterochromatin region. CT-like immunoreactivity was also observed at the plasma membrane but was only scarce. No reaction product was found when anti-CT serum pre-incubated with CT was used. In conclusion, these results bring evidence for a direct action of CT on lactotrope regulation in vitro as well as in intact animals.

Download Full-text

Effects of TRH on Pituitary Grafts in the Rat

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100073763 ◽

1973 ◽

Vol 31 ◽

pp. 664-665

Author(s):

Masataka Shiino ◽

Edward G. Rennels

Keyword(s):

Pituitary Gland ◽

Anterior Pituitary ◽

Chronic Treatment ◽

Saline Solution ◽

Male Rats ◽

Male Rat ◽

Cell Type ◽

Sprague Dawley ◽

Thyrotrophin Releasing Hormone ◽

Kidney Capsule

To date, many investigations have been reported on the ultrastructure of the “thyrotroph”. However, there is still confusion in regard to the ultrastructure of this cell type.In the present study, we observed ultrastructural alterations of anterior pituitary grafts following chronic treatment of the animals with synthetic thyrotrophin releasing hormone (TRH) (Schwarz-Mann). Male, Sprague- Dawley derived rats were hypophysectomized at 40 days of age. Seven days after the operation the anterior pituitary gland from a littermate male rat was transplanted under the kidney capsule. Thirty days following the transplantation, 100 pg of TRH was injected subcutaneously twice daily for 15 days (9:00 am and 4:00 pm). TRH was dissolved in 3% gelatin-saline solution at a concentration of 100 pg/0. 1 ml for each injection. As controls, hypophysectomized male rats with pituitary grafts were injected with 3% gelatin-saline solution by the same procedure.

Download Full-text

Immunocytochemical Localization of Secretogranin III in the Anterior Lobe of Male Rat Pituitary Glands

Journal of Histochemistry & Cytochemistry ◽

10.1177/002215540305100211 ◽

2003 ◽

Vol 51 (2) ◽

pp. 227-238 ◽

Cited By ~ 18

Author(s):

Yuko Sakai ◽

Masahiro Hosaka ◽

Yoshiki Hira ◽

Tatsuo Harumi ◽

Yoshiyuki Ohsawa ◽

...

Keyword(s):

Pituitary Gland ◽

Secretory Granule ◽

Endocrine Cells ◽

Secretory Granules ◽

Anterior Lobe ◽

Male Rat ◽

Secretory Proteins ◽

Chromogranin B ◽

Rat Pituitary ◽

Granule Membrane

Secretogranin III (SgIII) is one of the acidic secretory proteins, designated as granins, which are specifically expressed in neuronal and endocrine cells. To clarify its precise distribution in the anterior lobe of the rat pituitary gland, we raised a polyclonal antiserum against rat SgIII for immunocytochemical analyses. By immunohistochemistry using semithin sections, positive signals for SgIII were detected intensely in mammotropes and thyrotropes, moderately in gonadotropes and corticotropes, but not in somatotropes. The distribution pattern of SgIII in the pituitary gland was similar to that of chromogranin B (CgB), also of the granin protein family, suggesting that the expressions of these two granins are regulated by common mechanisms. The localization of SgIII in endocrine cells was confirmed by immunoelectron microscopy. In particular, secretory granules of mammotropes and thyrotropes were densely and preferentially co-labeled for SgIII and CgB in their periphery. Moreover, positive signals for SgIII were occasionally found in cells containing both prolactin and TSH in secretory granules. These lines of evidence suggest that SgIII and CgB are closely associated with the secretory granule membrane and that this membrane association might contribute to gathering and anchoring of other soluble constituents to the secretory granule membrane.

Download Full-text

The influence of adrenal hormone status on neuroendocrine peptides in the rat anterior pituitary gland

Journal of Endocrinology ◽

10.1677/joe.0.1270437 ◽

1990 ◽

Vol 127 (3) ◽

pp. 437-NP ◽

Cited By ~ 12

Author(s):

P. M. Jones ◽

D. J. O'Halloran ◽

M. A. Ghatei ◽

J. Domin ◽

S. R. Bloom

Keyword(s):

Pituitary Gland ◽

Anterior Pituitary ◽

Anterior Pituitary Gland ◽

Male Rat ◽

Mrna Levels ◽

Adrenal Hormone ◽

Rat Pituitary ◽

Hormone Status ◽

Anterior Pituitary Function ◽

Wet Weight

ABSTRACT Neuropeptide Y (NPY), neurotensin (NT), substance P (SP) and vasoactive intestinal peptide (VIP) are four structurally unrelated neuroendocrine peptides which affect anterior pituitary function. All four peptides appear to be locally synthesized in the anterior pituitary gland and have been shown to be regulated by thyroid and/or sex hormone status. We show here that NT, SP and VIP but not NPY are influenced by adrenal hormone status in the male rat pituitary gland. Adrenalectomy increased the content of VIP (35·4±4·0 (s.e.m.) vs control 11·9±1·1 pmol/g wet weight) but decreased that of SP (18·8±2·3 vs control 36·7 ±3·9 pmol/g wet weight). Adrenalectomy combined with castration decreased the content of SP (14·6±3·5 vs control 36·7±3·9 pmol/g wet weight) but had no effect on VIP content. Treatment with dexamethasone produced significant decreases in NT, SP and VIP contents (17·8±2·3 vs control 32·6±3·4 pmol/g wet weight, 5·5±0·9 vs control 36·7±3·9 pmol/g wet weight and 4·2±0·6 vs control 11·9±1·1 pmol/g wet weight respectively). The changes in pituitary peptide contents occurred in parallel with changes in mRNA levels, suggesting that alterations in glucocorticoid hormone status can alter the synthesis of these peptides. These results, together with the known effects of these neuroendocrine peptides suggest possible functions for locally produced SP and VIP in regulating the secretion of adrenocorticotrophin and/or other proopiomelanocortin-derived peptides. The differential effects of adrenalectomy and adrenalectomy combined with castration on VIP suggests that the regulation of this pituitary peptide is complex, and may be dependent, in part at least, on gonadal factors. Journal of Endocrinology (1990) 127, 437–444

Download Full-text

Ultrastructural evidence for oxytocin in the rat anterior pituitary gland

Acta Endocrinologica ◽

10.1530/acta.0.1170307 ◽

1988 ◽

Vol 117 (3) ◽

pp. 307-314 ◽

Cited By ~ 8

Author(s):

G. Morel ◽

J.-G. Chabot ◽

P. M. Dubois

Keyword(s):

Pituitary Gland ◽

Anterior Pituitary ◽

Secretory Granules ◽

Immune Serum ◽

Anterior Pituitary Gland ◽

Male Rat ◽

Posterior Lobe ◽

Cytoplasmic Matrix ◽

External Zone ◽

Ultrathin Sections

Abstract. OT is synthetized in the hypothalamus. These neurons project to the posterior lobe of the pituitary and the external zone of the median eminence. In order to localize OT in the male rat anterior pituitary we have used immunocytochemistry on ultrathin sections in target cell(s) obtained by cryoultramicrotomy. OT-like immunoreactivity was observed in lactotropes only. No immunoreactivity was observed in gonadotropes, somatotropes, corticotropes or thyrotropes. In lactotropes, immunoreactivity was localized at the plasma membrane level, in the cytoplasmic matrix and around the secretory granules, but not in the other organelles, and in the nucleus. No reaction was observed by using either non-immune serum or anti-OT serum incubated with OT. No modification of OT-like immunoreactivity was observed by using antiOT serum incubated with heterologous peptides. These results 1) provide immunocytological evidence for the presence of OT in the anterior pituitary gland; 2) indicate the presence of this peptide in one particular cell type, and 3) support the hypothesis that OT could have a direct participation in the regulation of the PRL release.

Download Full-text

ZUM WIRKUNGSMECHANISMUS VON AN FETEN ANTIMASKULIN WIRKSAMEN GESTAGENEN

Acta Endocrinologica ◽

10.1530/acta.0.045s139 ◽

1964 ◽

Vol 45 (4_Suppl) ◽

pp. S139-S153 ◽

Cited By ~ 43

Author(s):

K. Junkmann ◽

F. Neumann

Keyword(s):

Pituitary Gland ◽

Mechanism Of Action ◽

Androgen Receptors ◽

Male Rat ◽

Pregnant Rats ◽

Target Organs ◽

Causative Factors ◽

Competitive Action ◽

Androgenic Effect

ABSTRACT Experiments are described dealing with the mechanism of action of 6-chloro-Δ6-1,2α-methylene-17α-hydroxyprogesterone-acetate with regard to its anti-masculine effect on male rat foetuses, when administered to pregnant rats. It was shown that a marked direct anti-androgenic effect due to a competitive action on androgen receptors within the target organs, is probably the explanation of the mechanism of action. It was further shown that an oestrogenic effect or an appreciable inhibition of the pituitary gland respectively, can be ruled out as causative factors in the mechanism of action.

Download Full-text

Studies on the hypophysectomised ferret. II. - Spermatogenesis

Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character ◽

10.1098/rspb.1932.0083 ◽

1932 ◽

Vol 112 (775) ◽

pp. 146-152 ◽

Cited By ~ 3

Keyword(s):

Body Weight ◽

Pituitary Gland ◽

Reproductive Tract ◽

Complete Loss ◽

Male Rat ◽

Seminiferous Tubules ◽

Clear Cut ◽

Resulting Condition ◽

Made In ◽

Male Genital

Smith (1930) has shown that all parts of the reproductive tract of the male rat show pronounced atrophy after hypophysectomy. The testes are much reduced in size and are flabby. The seminiferous tubules show a corresponding diminution in size and all indications of spermatogenesis are absent. A more immediate effect of ablation of the pituitary gland is a complete loss of interest in the female. Richter and Wislocki (1930) also noted atrophy of the male genital organs of the rat after hypophysectomy, but in no great detail. Hypophysectomy has not yet been performed on a species in which the male shows a clear cut anœstrous period such as is found in the male ferret (Allanson, 1932). The present work was undertaken to find out if the testes of the ferret react to hypophysectomy in the same way as those of the rat, and to compare the resulting condition of the testes with that found during anœstrus. Further light on the activity of the pituitary body during anœstrus might thus be obtained. In addition, it was hoped to determine the rate of regression after hypophysectomy and to compare this with that found at the end of the breeding season. No attempt will be made in this or the following paper to deal with the general effects of hypophysectomy, but it may be mentioned that loss of body weight, if any, was slight during the time covered by these experiments.

Download Full-text

Secretogranin II binds to secretogranin III and forms secretory granules with orexin, neuropeptide Y, and POMC

Journal of Endocrinology ◽

10.1677/joe-08-0531 ◽

2009 ◽

Vol 202 (1) ◽

pp. 111-121 ◽

Cited By ~ 26

Author(s):

Kikuko Hotta ◽

Masahiro Hosaka ◽

Atsushi Tanabe ◽

Toshiyuki Takeuchi

Keyword(s):

Body Weight ◽

Neuropeptide Y ◽

Secretory Granules ◽

Immunohistochemical Analysis ◽

Mrna Levels ◽

Weight Changes ◽

Body Weight Changes ◽

Hypothalamic Area ◽

Double Labeling ◽

Secretogranin Ii

Functional variations in the secretogranin III (SCG3) gene are associated with susceptibility to obesity. SCG3 forms secretory granules with orexin, melanin-concentrating hormone (MCH), neuropeptide Y (NPY), and POMC in the hypothalamus. In this study, we screened proteins for SCG3-binding activity and identified secretogranin II (SCG2) using a yeast two-hybrid system. Immunoprecipitation revealed that SCG2 interacts with SCG3. In situ hybridization and immunohistochemistry indicated that SCG2 was highly expressed in the lateral hypothalamic area, paraventricular nucleus, and arcuate nucleus of the hypothalamus. Double-labeling immunohistochemical analysis demonstrated that SCG2 was expressed in orexin-, MCH-, NPY-, and POMC-expressing neurons. SCG2 was also coexpressed with SCG3. Upon introduction into neuroblastoma cells, SCG2 was expressed in the cytosol and formed granule-like structures with SCG3, orexin, NPY, or POMC. SCG3 bound to POMC; however, it did not bind to orexin, MCH, or NPY. By contrast, SCG2 formed aggregates with orexin, MCH, NPY, and POMC. SCG2 may act as a hormone carrier for orexin, MCH, NPY, and POMC by binding with SCG3, which targets proteins to the secretory granules. SCG2 mRNA levels increased along with those of SCG3, orexin, MCH, and NPY after a 24-h fast, suggesting that the SCG2/SCG3 system may respond in an adaptive manner to acute body weight changes. However, this SCG2/SCG3 system appears to be unresponsive to chronic body weight changes, such as diet-induced obesity or obesity in ob/ob mice. We suggest that SCG2, as well as SCG3, may be a potential regulator of food intake based on its capacity to accumulate appetite-related hormones into secretory granules.

Download Full-text