Microtubules assembled in vitro were bound to purified porcine pituitary secretory granules and to isolated granule membranes. The interaction between microtubules and whole secretory granules was demonstrated by alteration in the sedimentation properties of the microtubules. Incubation of secretory granules with mierotubules resulted in pelleting of microtubules which increased as a function of the number of granules added. Binding was quantitated by measurement of the tubulin remaining in the supernate after centrifugation. The interaction of secretory granules and microtubules was inhibited by nucleoside triphosphates and augmented by adenosine 5'-monophosphate and adenosine. When depolymerized protein from microtubules was incubated with secretory granules, the granules did not appear to bind the soluble tubulin dimer present in these preparations. However, the high molecular weight protein associated with microtubules was adsorbed by secretory granules during the binding process. Incubation of isolated secretory granule membranes with microtubules followed by centrifugation to density equilibrium in a discontinuous sucrose density gradient caused pelleting of the membranes, which otherwise banded higher in the gradient. The visible alteration in membrane sedimentation was confirmed by measurements of the membrane-associated magnesium-ATPase activity and by a shift in radioactivity in iodinated membrane preparations. Our data suggest a role for microtubules in the intracellular movement of secretory granules; this movement is perhaps brought about by dynein-like cross bridges which link the tubulin backbone and granule surface.In recent years, numerous studies have suggested that microtubule integrity is essential for normal secretion to occur (8, 11, 16, 22-24, 27, 28, 42, 43, 48). The bulk of the evidence for this proposition rests upon the ability of the microtubuledisruptive agents vinblastine and colchicine (49) to block the release of a variety of secretory products. Despite the general agreement that microtubules are necessary for secretion, their exact role is unclear.Those cells which release proteins, peptides, and neurotransmitters package the product in the Golgi apparatus within membrane-bounded vesicles or granules. Upon the appropriate stimulus, the granule membrane fuses with the cell membrane and exocytosis occurs. Movement of score-
influence of serum triiodothvronine (T3) and thyroxine (T4) concentrations on the release of prolactin in man was studied by determining the prolactin response to synthetic thyrotropin-releasing hormone (TRH) in hypothyroid and hyperthyroid patients before and after correction of their serum thyroid hormone abnormalities. The maximum increment in serum prolactin above the basal level (maximum A prolactin) was used as the index of response to TRH. In 12 patients with primary hypothyroidism, the maximum A prolactin in response to TRH fell from 100.5± 29.1 ng/ml (mean +SEM) before treatment to 36.1±6.0 ng/ml (P < 0.01) during the 4th Nk of treatment with 30 jug T3 + 120 jug T4 daily. The mean serum T3 level increased from 57±8 to 138+10 ngl100 nml! and the mean serum T4 level increased from 3.0±0.4 to 7.2±0.4 Ag/lOO ml during this treatment. In eight normal subjects the maximum Aprolactin in response to TRH was not significantly different during the 4th wk of treatment with 30 Ag T3 + 120 /g T4 daily from the response before treatment. In 10 patients with hvperthyroidism, the maximum Aprolactin in response to TRH increased from 14.2±2.9 ng/ml before treatment to 46.9±6.7 nig/ml (P < 0.001) during antithyroid treatment. The mean serum T3 level fell from 313±47 to 90±8 ng/100 ml, and the mean serum T4 level fell from 20.8±2.5 to 6.8+ 0.6 Ig/100 ml during this treatment. These results show that changes from normal serum levels of T3 and T4 are associated with changes in prolactin responses to TRH; subnormal serum levels of T3 and T4 increase TRH-induced prolactin release,
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.