Development and cytodifferentiation of the rabbit pars intermedia. II. Neonatal to adult.
Material from pars intermedia obtained from rabbits ranging from the second week post-partum to the adult stage, and including specimens from pregnant animals, was studied. The rate of cell division became greatly reduced early in postnatal) development. The commonest type of cell (the pars intermedia-glandular cell) becomes increasingly PAS-positive during the early stages of development. Although by 35 days differentiation of all the ACT-type cells is complete, the pars intermedia-glandular cells take as long as 53 days to mature. The epithelioid border of the hypophysial cleft persists throughout life, commonly containing dark cells. A ciliary fringe frequently appears in neonates and persists in pregnancy. Possible functions of such cilia are discussed. Throughout development the fine structure of the vasculature was studied. Secretory granules resembling those within the cells were seen in and around the blood vessels, and the mode of endocrine secretion in the pars intermedia tissue is discussed. The pars intermedia-glandular cells of the pregnant rabbits appeared hyperactive. The functional significance of the mammalian pars intermedia is discussed. (+info)
Melatonin inhibits release of luteinizing hormone (LH) via decrease of [Ca2+]i and cyclic AMP.
The role of [Ca2+]i and cAMP in transduction of the melatonin inhibitory effect on GnRH-induced LH release from neonatal rat gonadotrophs has been studied, because melatonin inhibits the increase of both intracellular messengers. Treatments increasing Ca2+ influx (S(-) Bay K8644 or KCI) or cAMP concentration (8-bromo-cAMP or 3-isobutyl-1-methylxanthine) potentiated the GnRH-induced LH release and partially diminished the inhibitory effect of melatonin. Combination of the treatments increasing cAMP and calcium concentrations blocked completely the melatonin inhibition of LH release. The combined treatment with 8-bromo-cAMP and S(-) Bay K8644 also blocked the melatonin inhibition of GnRH-induced [Ca2+]i increase in 89 % of the gonadotrophs, while any of the treatments alone blocked the melatonin effect in about 25 % of these cells. These observations suggest that a cAMP-dependent pathway is involved in regulation of Ca2+ influx by melatonin and melatonin inhibition of LH release may be mediated by the decrease of both messengers. (+info)
Secretagogue-induced exocytosis recruits G protein-gated K+ channels to plasma membrane in endocrine cells.
Stimulation-regulated fusion of vesicles to the plasma membrane is an essential step for hormone secretion but may also serve for the recruitment of functional proteins to the plasma membrane. While studying the distribution of G protein-gated K+ (KG) channels in the anterior pituitary lobe, we found KG channel subunits Kir3.1 and Kir3.4 localized on the membranes of intracellular dense core vesicles that contained thyrotropin. Stimulation of these thyrotroph cells with thyrotropin-releasing hormone provoked fusion of vesicles to the plasma membrane, increased expression of Kir3.1 and Kir3.4 subunits in the plasma membrane, and markedly enhanced KG currents stimulated by dopamine and somatostatin. These data indicate a novel mechanism for the rapid insertion of functional ion channels into the plasma membrane, which could form a new type of negative feedback control loop for hormone secretion in the endocrine system. (+info)
Developmental changes in LH secretion by male pituitaries in vitro: from the infantile to adult period.
The secretion of LH from the anterior pituitary of male rats was studied at different periods of postnatal development. According to an established classification we used rats 14 (infantile), 23 (juvenile), 45 (pubertal) and 90 (adult) days old. By using an in vitro incubation system, both basal and stimulated LH secretion were studied in the same gland. Age-related differences were observed in basal LH secretion, with juvenile and pubertal pituitaries showing higher secretion compared with infantile and adult pituitaries. However, the GnRH-induced secretory response was significantly higher in the infantile rats than in other ages. LH secretion was also studied in primary cultures from infantile or adult pituitaries. In 24 and 48 h cultures, infantile cells showed a significantly larger response to GnRH than that of adult cells. In the infantile pituitary LH-immunopositive cells showed differences in size at different locations in the gland. At the periphery of the lobes the predominant cells were smaller and angular shaped, whereas in the center of the gland the majority of the cells were ovoid shaped. In the adult pituitary, the predominant LH-positive cells were ovoid in shape and larger in size. Furthermore, 10% more LH-positive cells were observed in infantile pituitaries. On the basis of these data we propose that at the infantile period the male rat pituitary has two populations of LH-secreting cells, one with adult secretory function and shape and a second with increased sensitivity to GnRH and with a morphology atypical of the adult cell. The results presented support the hypothesis that the infantile period is a transitional stage in the rat pituitary development. (+info)
The neuroendocrine protein 7B2 is required for peptide hormone processing in vivo and provides a novel mechanism for pituitary Cushing's disease.
The neuroendocrine protein 7B2 has been implicated in activation of prohormone convertase 2 (PC2), an important neuroendocrine precursor processing endoprotease. To test this hypothesis, we created a null mutation in 7B2 employing a novel transposon-facilitated technique and compared the phenotypes of 7B2 and PC2 nulls. 7B2 null mice have no demonstrable PC2 activity, are deficient in processing islet hormones, and display hypoglycemia, hyperproinsulinemia, and hypoglucagonemia. In contrast to the PC2 null phenotype, these mice show markedly elevated circulating ACTH and corticosterone levels, with adrenocortical expansion. They die before 9 weeks of severe Cushing's syndrome arising from pituitary intermediate lobe ACTH hypersecretion. We conclude that 7B2 is indeed required for activation of PC2 in vivo but has additional important functions in regulating pituitary hormone secretion. (+info)
Some observations on the ultrastructure of the adenohypophysis of the Plains viscacha (Lagostomus maximus).
The ultrastructural appearance of the pars distalis of the Plains viscacha is described. Of particular interest are the prolactin cells and stellate cells and the intercellular cysts or channels which may be part of a transport system for hormones. (+info)
Cyto-differentiation and portal vascular development in the mouse adenohypophysis.
Pituitaries of fetal and postnatal (15 days p.c.-28 days p.n.) and adult (male) mice were studied by light and electron microscopy to correlate the developmental pattern of the hypothalamo-hypophysial vascular system with the time of onset of function of the adenohypophysis. The superior and anterior regions of the adenohypophysis become vascularized at 17 days p.c., when portal vessels extend from oral primary plexus to the pars distalis for the first time. Adenohypophysial vascularity and the number of portal vessels steadily increase to reach the adult pattern at 5 days p.n. At 1 day p.n. deep capillary loops appear in the caudal regions of the oral primary plexus; a capillary (tangential) plexus underlies the ependymal lining of the third ventricle by 6 days p.n. Superficial capillary loops were not observed until the third postnatal week. Granulation of secretory cells commences at 16 days p.c., predominantly in the upper and anterior adenohypophysis; at 17 days thyrotropes, gonadotropes and corticotropes are recognizable and by morphological criteria appear actively secretory on days 17-18 p.c., although few appear active at 19 days p.c. and 1 day p.n. Somatotropes are first seen at 18 days p.c., predominantly in the central and lateral regions of the pars distalis. Active secretory cells increase in number over the period 2-10 days p.n., but after 11 days p.n. thyrotropes and corticotropes seem to become progressively less active; fewer gonadotropes are seen after 15 days p.n., and these apparently become progressively less active from day 19. Most somatotropes appear active until 28 days p.n. The observations suggest that hypothalamic control of adenohypophysial function may exist in the mouse from 17 days p.c. (+info)
Glucocorticoid block of protein kinase C signalling in mouse pituitary corticotroph AtT20 D16:16 cells.
1. The regulation of large conductance calcium- and voltage-activated potassium (BK) currents by activation of the protein kinase C (PKC) and glucocorticoid signalling pathways was investigated in AtT20 D16:16 clonal mouse anterior pituitary corticotroph cells. 2. Maximal activation of PKC using the phorbol esters, 4beta-phorbol 12-myristate, 13-acetate (PMA), phorbol 12, 13 dibutyrate (PDBu) and 12-deoxyphorbol 13-phenylacetate (dPPA) elicited a rapid, and sustained, inhibition of the outward steady-state voltage- and calcium- dependent potassium current predominantly carried through BK channels. 3. The effect of PMA was blocked by the PKC inhibitors bisindolylmaleimide I (BIS; 100 nM) and chelerythrine chloride (CHE; 25 microM) and was not mimicked by the inactive phorbol ester analogue 4alpha-PMA. 4. PMA had no significant effect on the 1 mM tetraethylammonium (TEA)-insensitive outward current or pharmacologically isolated, high voltage-activated calcium current. 5. PMA had no significant effect on steady-state outward current in cells pre-treated for 2 h with 1 microM of the glucocorticoid agonist dexamethasone. Dexamethasone had no significant effect on steady-state outward current amplitude or sensitivity to 1 mM TEA and did not block PMA-induced translocation of the phorbol ester-sensitive PKC isoforms, PKCalpha and PKCepsilon, to membrane fractions. 6. Taken together these data suggest that in AtT20 D16:16 corticotroph cells BK channels are important targets for PKC action and that glucocorticoids inhibit PKC signalling downstream of PKC activation. (+info)