INTERACTION OF α-MELANOCYTE-STIMULATING HORMONE, MELATONIN, CYCLIC AMP AND CYCLIC GMP IN THE CONTROL OF MELANOGENESIS IN HAIR FOLLICLE MELANOCYTES IN VITRO

1981 ◽  
Vol 90 (1) ◽  
pp. 89-96 ◽  
Author(s):  
BRIAN WEATHERHEAD ◽  
ANN LOGAN

In short-term (48 h) cultures of hair follicles α-melanocyte-stimulating hormone (α-MSH) and cyclic AMP stimulated melanogenesis through an increase in tyrosinase activity. In contrast cyclic GMP mimicked the effects of melatonin by inhibiting melanin production without causing a concomitant decrease in tyrosinase activity. Both cyclic GMP and melatonin blocked the stimulatory effects of cyclic AMP and α-MSH on melanin production but they left the increased levels of tyrosinase activity unaffected. Phosphodiesterase inhibitors (3-isobutyl-1-methylxanthine and papaverine) simultaneously stimulated tyrosinase activity and inhibited melanin production, presumably by allowing endogenous cyclic AMP and cyclic GMP to accumulate intracellularly. It is suggested that whereas MSH stimulates melanogenesis through a cyclic AMP-dependent mechanism there must also be an inhibitory cyclic GMP-dependent mechanism, perhaps activated by melatonin, which operates at some post-tyrosinase step in the melanin biosynthetic pathway.

1981 ◽  
Vol 91 (3) ◽  
pp. 501-507 ◽  
Author(s):  
ANN LOGAN ◽  
BRIAN WEATHERHEAD

α-Melanocyte-stimulating hormone (α-MSH) has been shown to act directly on the mammalian melanocyte in short-term cultures of hair follicles obtained from the Siberian hamster. Melanogenesis was stimulated through an increase in tyrosinase activity which resulted in an increase in melanin production. The response of hair follicle melanocytes to α-MSH occurred only in follicles taken from moulting animals, implying that they show a discontinuous expression of MSH receptors during the hair follicle growth cycle. Synthetic 1–24 ACTH had no effect on melanogenesis regardless of whether the follicles came from moulting or non-moulting animals. The pineal peptide, [8-arginine]-vasotocin (AVT), inhibited melanin production without a concomitant decrease in tyrosinase activity. In this respect AVT resembled melatonin, although AVT showed a potency ratio of less than half on a molar basis. The action of AVT, like that of melatonin, must ultimately be on some post-tyrosinase step in melanin biosynthesis. In these hair follicle melanocytes AVT seems to bind to specific receptors since neither of the closely related peptides, oxytocin and [8-arginine]-vasopressin, displayed any activity in our culture system.


1976 ◽  
Vol 68 (2) ◽  
pp. 283-287 ◽  
Author(s):  
BRIDGET I. BAKER

SUMMARY Various agents were tested for their ability to oppose the stimulatory effect of dibutyryl cyclic AMP on the release of the melanocyte-stimulating hormone from the rat neuro-intermediate lobe in vitro. Only dopamine exhibited an inhibitory effect; serotonin, γ-aminobutyric acid, tocinoic acid, tocinamide, the tripeptide Pro-Leu-Gly-NH2 and dibutyryl cyclic GMP were all ineffective.


1983 ◽  
Vol 50 (04) ◽  
pp. 804-809 ◽  
Author(s):  
Torstein Lyberg

SummaryHuman monocytes in vitro respond to various agents (immune complexes, lectins, endotoxin, the divalent ionophore A 23187, 12-0-tetradecanoyl-phorbol 13-acetate [TPA], purified protein derivative [PPD] of Bacille Calmette-Guerin) with an increased synthesis of the protein component of thromboplastin. The effect of cyclic AMP and cyclic GMP on this response has been studied. Dibutyryl-cyclic AMP, prostaglandin E1 and the phosphodiesterase inhibitors 3-butyl-1-methyl-xanthine (MIX) and rac -4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 201724), separately and in combination have a pronounced inhibitory effect on the response to immune complexes and PPD, and a moderate effect on the response to endotoxin and lectins. The effect on TPA response and on the response to A 23187 was slight. Dibutyryl-cyclic GMP (1 mM) gave a slight inhibition of the TPA arid IC response, but had essentially no effect on the response to other inducers. The intracellular cAMP level increased when monocytes were incubated with IC, TPA or A 23187 followed by a decrease to basal levels within 1-2 hr, whereas lectin (PHA) and PPD did not induce such changes. The cAMP response to endotoxin varied. Stimulation with IC induced an increase in monocyte cGMP levels, whereas the other stimulants did not cause such changes.


1986 ◽  
Vol 111 (2) ◽  
pp. 225-232 ◽  
Author(s):  
S. A. Burchill ◽  
A. J. Thody

ABSTRACT Skin tyrosinase activity increases during hair growth in C3H–HeA*vy mice and reaches higher levels in young (30- to 35-day-old) mice when the hair follicular melanocytes synthesize the black pigment, eumelanin, than in older (6-month-old) mice when they produce the golden yellow pigment, phaeomelanin. To examine the regulation of the melanocytes at these different stages we have compared the effect of α-MSH and other agents that act, through cyclic AMP-dependent mechanisms, on skin tyrosinase activity in both young and old mice during hair growth, initiated by plucking. Daily administration of α-MSH, isoprenaline or theophylline increased coat darkness, and skin tyrosinase activity in the younger mice 7–9 days after plucking, but they were ineffective in the older mice. Similarly α-MSH, 8-bromo-cyclic AMP or theophylline increased tyrosinase activity in skin explants from the younger mice incubated for up to 24 h but had no effect in explants from older mice. Cyclic GMP had no effect on tyrosinase activity in skin explants from both young and old mice. It is suggested that whereas cyclic AMP-dependent mechanisms may operate to regulate tyrosinase activity in the hair follicular melanocytes of younger mice that produce eumelanin these systems may not operate in the older mice when these melanocytes synthesize phaeomelanin. Phaeomelanin synthesis, unlike that of eumelanin, may not depend upon tyrosinase and its regulation by cyclic AMP and this could explain the low levels of this enzyme in the skin and its failure to respond to α-MSH and other activators of the cyclic AMP system during periods of phaeomelanin production. J. Endocr. (1986) 111, 225–232


1983 ◽  
Vol 97 (1) ◽  
pp. 43-49 ◽  
Author(s):  
U. Zor ◽  
B. Strulovici ◽  
R. Braw ◽  
H. R. Lindner ◽  
A. Tsafriri

The aim of this study was to search for direct biochemical effects of highly purified FSH on isolated ovarian follicular theca in vitro. Granulosa cells (GC; approximately 1 × 105 cells per follicle) were flushed from isolated follicles of pro-oestrous rats. The remaining theca layer and the isolated GC were incubated with highly purified ovine FSH. Prostaglandin E (PGE) accumulation was measured by radioimmunoassay. Follicle-stimulating hormone induced a 15-fold increase in PGE accumulation over the basal level in the follicular theca, the stimulated rate exceeding threefold that observed in the GC fraction derived from the same follicle. Follicle-stimulating hormone caused no significant increase in cyclic AMP level or steroidogenesis in the theca layer, but was active on these parameters in the GC. In contrast, LH increased the accumulation of cyclic AMP, progesterone and testosterone, as well as of PGE, in follicular theca. Exogenous 8-bromo cyclic AMP or cyclic GMP also stimulated PGE production in follicular theca or GC, but FSH was without any effect on the level of endogenous cyclic GMP in GC or follicular theca. Antibodies to FSH prevented the effect of FSH (but not that of LH) on PGE formation by follicular theca and GC, while antibodies to the β-subunit of LH blocked the effect of LH but not of FSH. We conclude that highly purified FSH has a stimulatory effect on PGE formation by the follicular theca.


1989 ◽  
Vol 92 (4) ◽  
pp. 551-559
Author(s):  
A. Slominski ◽  
G. Moellmann ◽  
E. Kuklinska

In Bomirski Ab amelanotic hamster melanoma cells, L-tyrosine and/or L-dopa induce increases in tyrosinase activity as well as synthesis of melanosomes and melanin. L-tyrosine also modifies melanocyte-stimulating hormone (MSH) binding. In this paper we show that in the Bomirski amelanotic melanoma system MSH and agents that raise intracellular cyclic AMP induce dendrite formation, inhibit cell growth, and cause substantial increases in tyrosinase activity without inducing melanin synthesis. Tyrosinase activity is detected only in broken cell preparations, or cytochemically in fixed cells. In the continued absence of mature melanosomes, the induced enzyme remains in elements of the trans-Golgi reticulum. Comparative measurements of cyclic AMP in amelanotic and tyrosine-induced melanotic cells show similar basal levels. L-tyrosine and L-dopa have little or no effect, whereas MSH may cause a 1000% peak increase in cyclic AMP levels both in amelanotic and melanotic cells. None of these agents influences cyclic GMP or inositol trisphosphate (InsP3) levels. In agreement with the InsP3 assays, phorbol ester (TPA) has no effect on melanization, tyrosinase activity or cell proliferation. In conclusion, in the Bomirski amelanotic melanoma, MSH induces only partial cell differentiation associated with raised levels of cyclic AMP. Induction of melanosome synthesis and melanization by L-tyrosine or L-dopa appear to follow pathways unrelated to cyclic AMP, cyclic GMP or InsP3.


1974 ◽  
Vol 63 (3) ◽  
pp. 533-538 ◽  
Author(s):  
BRIDGET I. BAKER

SUMMARY A method for measuring melanocyte-stimulating hormone (MSH) in rat neurointermediate lobe in vitro and in incubation medium, using polyacrylamide gel electrophoresis, is described. Using this technique, it was shown that dibutyryl cyclic AMP increased the release of MSH in vitro, the degree of stimulation depending on the concentration of the nucleotide. The effect of low concentrations of the nucleotide was potentiated by theophylline.


1994 ◽  
Vol 107 (1) ◽  
pp. 205-211 ◽  
Author(s):  
G. Hunt ◽  
C. Todd ◽  
J.E. Cresswell ◽  
A.J. Thody

Although melanocyte stimulating hormone (MSH) peptides are known to stimulate pigmentation in man, previous reports suggest that human melanocytes are relatively unresponsive to these peptides in vitro. This may be related to the conditions under which the melanocytes were cultured. Thus, we have re-investigated the in vitro effects of MSH peptides using human melanocytes cultured in the absence of artificial mitogens. Human melanocytes were incubated with alpha-MSH or its potent analogue Nle4Dphe7 alpha-MSH for 3 days. After 18 hours, melanocyte morphology had evolved from mainly bipolar to dendritic in approximately 66% of cultures. Nle4DPhe7 alpha-MSH produced dose-related increases in both tyrosinase activity and melanin content although the degree of response was variable and tyrosinase activity was the relatively more responsive to the peptide. Similar results were obtained with alpha-MSH, but, although the effect on melanin content was similar to that of Nle4DPhe7 alpha-MSH, the effect on tyrosinase activity was less marked. The preliminary EC50 values for the actions of the MSH peptides suggest that they may be equipotent in their actions on human melanocytes. In addition, we have demonstrated that the common melanocyte mitogens 12-O-tetradecanoyl phorbol-13-acetate (TPA) and cholera toxin affect basal melanogenesis and modulate the effects of the MSH peptides. However, not all melanocyte cultures showed melanogenic responses to the MSH peptides. Ability to respond was unrelated to basal levels of tyrosinase activity or melanin content. In at least some cultures, morphological and melanogenic responses appear to be independent of one another.(ABSTRACT TRUNCATED AT 250 WORDS)


1973 ◽  
Vol 57 (3) ◽  
pp. 845-858 ◽  
Author(s):  
Bruce Magun

Photomicrography and reflectance microphotometry were used to monitor melanosome movement in frog skin melanocytes in vitro in response to hormonal stimulation and cytochalasin B (CB). Melanocyte-stimulating hormone (MSH), theophylline, and dibutyryl cyclic AMP (DiBcAMP) induced melanosome dispersion (darkening) which was promptly arrested by cytochalasin B in concentrations of 5–20 µg/ml. Melanosome aggregation (skin lightening) occurred only after removal of the darkening agent (MSH, theophylline, or DiBcAMP) and proceeded in the presence or absence of CB. When CB was added to darkened skins, they did not lighten and melanosomes remained in the dispersed state. Use of CB has permitted the dissection of cyclic AMP-mediated melanosome dispersion into two distinct events. The first, induction of melanosome dispersion, is CB sensitive. The second action of intracellular cyclic AMP involves an uncoupling of the centripetal motive force, and is CB insensitive. In the latter process, production of cyclic AMP appears to produce the same result as application of microtubule-disrupting agents.


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