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A M Kaye

Publications and source records attributed to A M Kaye.

At least 37 records · Page 2Linked to original sources
PubMed1994

Stimulation by insulin-like growth factor-I of creatine kinase activity in skeletal-derived cells and tissues of male and female rats.

Insulin-like growth factor-I (IGF-I) has been reported to mediate the effects of oestradiol-17 beta in the osteoblast-like osteosarcoma cell line ROS 17/2.8 and to stimulate directly cell proliferation in cell cultures derived from rat calvaria. Few data are available on the role of IGF-I in androgen stimulation of cultured skeletal cells and in oestrogen and androgen stimulation of bone and cartilage in vivo. The purpose of the present study was to compare the effect of IGF-I in rats in vivo with its effect in vitro on calvarial bone cells from females (responding only to oestrogens) and from males (responding only to androgens, such as testosterone and dihydrotestosterone). We found that IGF-I stimulated, in a dose- and time-dependent manner, the specific activity of creatine kinase (CK, a marker of skeletal cell division), in both female and male calvarial bone cells, in ROS 17/2.8 cells and in epiphyseal cartilage cell cultures. Maximal stimulation occurred at 30 or 100 nM within 1-2 h after stimulation. In ROS 17/2.8 cells, IGF-I stimulated [3H]thymidine incorporation, after 22 h of treatment, in parallel with CK activity. IGF-II, at higher doses than IGF-I (maximal stimulation at 300 nM), stimulated CK specific activity in female- and male-derived calvarial cell cultures. When IGF-I (50 nM) was applied together with oestradiol-17 beta (30 nM) or with dihydrotestosterone (300 nM) there was no additional response in the cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Sex-specific response of bone cells to gonadal steroids: modulation in perinatally androgenized females and in testicular feminized male rats.

We have found previously that rat diaphyseal bone in vivo, as well as rat embryo calvaria cells in culture, show a sex-specific response to gonadal steroids in stimulation of creatine kinase (CK)-specific activity, and the rate of [3H]thymidine incorporation into DNA; male-derived cells responded only to testosterone or to dihydrotestosterone (DHT), whereas female-derived cells were stimulated exclusively by estradiol (E2). In this study, we tested whether developmental hormone manipulation could alter this sex specificity. We showed that diaphyseal bone of prenatally or neonatally androgenized female rats responds to a single injection of either E2 (5 micrograms/rat) or DHT (50 micrograms/rat) at 3-4 weeks postandrogenization. This response of androgenized female diaphyseal bone to androgen gradually declines; 3 months posttreatment, diaphyseal bone no longer responds to DHT and reverts to its original sex specificity. Rat embryo calvaria cell cultures prepared from female fetuses androgenized in utero showed the same lack of hormonal specificity, that is, the cells responded to both E2 (30 nM) or DHT (300 nM). Cells derived from the male siblings of the prenatally androgenized rats were not affected and responded only to DHT. In contrast to experiments in utero, in vitro administration of testosterone (1 microM) or E2 (1 microM) to calvaria cells from female embryos failed to cause the cells to respond to DHT. Androgen receptor-deficient (Tfm) male rats, which have approximately 10% of the normal response to androgens, also showed a response to both testosterone and E2 in comparison to their normal male siblings, whose bones responded only to androgens.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen-Insensitivity Syndrome↗
PubMed1992

Responsiveness of the 5'-flanking region of the brain type isozyme of creatine kinase to estrogens and antiestrogen.

The brain type isozyme of creatine kinase (CKB) has proven to be a useful early marker for the action of steroid and other hormones. An increase in the steady state level of mRNA for CKB was found within 30 min after estrogen stimulation of immature rat uteri. Cycloheximide treatment did not inhibit CKB induction. In order to study the molecular mechanism of this induction, 2.9 kb of the 5'-flanking region of CKB fused with the CAT reporter gene was cotransfected into ROS 17/2.8 and HeLa cells along with an expression plasmid for the human estrogen receptor. 17 beta-Estradiol at 10(-8) M or greater concentrations and the antiestrogen tamoxifen at 10(-6) M stimulated CAT activity. When given simultaneously with 17 beta-estradiol, tamoxifen showed a synergistic effect.

Animals↗
PubMed1991

Stimulation of cell proliferation in skeletal tissues of the rat by defined parathyroid hormone fragments.

We have found, in previous studies in vitro using skeletal derived cell cultures, that mid-region fragments of human parathyroid hormone (hPTH) stimulate [3H]thymidine incorporation into DNA and increase the specific activity of the brain-type isoenzyme of creatine kinase (CK). These changes occurred without an increase in cyclic AMP formation which is linked to bone resorption. In this study, we found that the mid-region fragment hPTH-(28-48) stimulated CK activity in diaphysis, epiphysis and kidney in a time- and dose-dependent manner, parallel to the effects of the whole molecule bovine (b)PTH-(1-84) and the fully active fragment hPTH-(1-34). The increase caused by hPTH-(28-48) at a dose of 1.25 micrograms/rat was not less than the 2-fold increase caused by a roughly equimolar concentration bPTH-(1-84). A significant increase was reached at 1 h after intraperitoneal injection in all cases. All three sequences of PTH caused an increase in [3H]thymidine incorporation into DNA in diaphysis and epiphysis, but not in kidney, 24 h after injection. A fragment further towards the C-terminal, hPTH-(34-47), was inactive compared with an equimolar concentration of the fragment hPTH-(25-39), which stimulated both CK activity and DNA synthesis. These results in vivo are in line with previous findings in vitro; they provide further support for the suggestion that mid-region fragments of the PTH molecule could be used to induce bone formation without incurring the deleterious effect of bone resorption.

Animals↗
PubMed1991

Regulation of proliferation of rat cartilage and bone by sex steroid hormones.

We have demonstrated previously that 17 beta-estradiol (E2) stimulates proliferation of skeletal tissues, both in vivo and in vitro, as measured by increased DNA synthesis and creatine kinase (CK) specific activity. The effect of E2 on bone is sex specific. E2 is active only in females and androgens only in males. By contrast, in cartilage of both sexes, dihydrotestosterone (DHT) as well as E2 stimulates CK specific activity and DNA synthesis. In bone, we find that sex steroids stimulate skeletal cell proliferation in gonadectomized as well as in immature rats. Ovariectomized (OVX) rats, between 1 and 4 weeks after surgery, show stimulation of CK by E2. The basal activity and response of CK changes with the varying endogenous levels of E2 in cycling rats, in which the highest basal activity is at proestrus and estrus and the highest response is in diestrus. In rats of all ages tested, both the basal and stimulated specific activity of CK is higher in diaphysis and epiphysis than in the uterus, or in the adipose tissue adjacent to the uterus, which has a response similar to that of the uterus itself. The effect of E2 in vivo, and in chrondroblasts and osteoblasts in vitro, is inhibited by high levels of the antiestrogen tamoxifen which, by itself, in similar high concentrations, shows stimulatory effects. In addition to the sex steroids, skeletal cells are also stimulated by secosteroid and peptide calciotrophic hormones. The interactions of the sex steroids with these hormones modulate the response of cartilage and bone cells to both sex steroids and the other calciotrophic hormones. These results provide the first steps towards understanding the regulation of bone cell proliferation and growth by the concerted action of a variety of hormones and growth factors.

Animals↗
PubMed1990

Stimulation by defined parathyroid hormone fragments of cell proliferation in skeletal-derived cell cultures.

We have reported previously that parathyroid hormone (PTH) acts on cultured bone cells to stimulate creatine kinase (CK) activity and [3H]thymidine incorporation into DNA via phosphoinositide turnover, in addition to its other actions via increased cyclic AMP production. We also found that mid-region fragments of PTH stimulate [3H]thymidine incorporation into avian chondrocytes. In the present study of mammalian systems, we demonstrate differential effects of defined synthetic PTH fragments on CK activity and DNA synthesis, as compared with cyclic AMP production, in osteoblast-enriched embryonic rat calvaria cell cultures, in an osteoblast-like clone of rat osteosarcoma cells (ROS 17/2.8) and in chondroblasts from rat epiphysial cartilage cell cultures. Unlike full-length bovine (b)PTH-(1-84) or the fully effective shorter fragment human (h)PTH-(1-34), fragments lacking the N-terminal region of the hormone did not increase cyclic AMP formation, whereas they did stimulate increases in both DNA synthesis and CK activity. Moreover, the PTH fragment hPTH-(28-48) at 10 microM inhibited the increase in cyclic AMP caused by 10 nM-bPTH-(1-84). The increase of CK activity in ROS 17/2.8 cells caused by bPTH-(1-84) or hPTH-(28-48) was completely inhibited by either cycloheximide or actinomycin D, as was shown previously for rat calvaria cell cultures. These results indicated the presence of a functional domain of PTH in the central part of the molecule which exerts its mitogenic-related effects on osteoblast- and chondroblast-like cells in a cyclic AMP-independent manner. Since cyclic AMP formation by PTH leads to bone resorption, specific mid-region fragments of PTH might prove suitable for use in vivo to induce bone formation without concomitant resorption.

Animals↗
PubMed1990

Reciprocal modulation by sex steroid and calciotrophic hormones of skeletal cell proliferation.

We have demonstrated previously that 17 beta-estradiol (E2) stimulates cell proliferation in skeletal tissues, as measured by increased DNA synthesis and creatine kinase (CK) specific activity, and that calciotrophic hormones modulate E2 activity in rat osteoblastic sarcoma cells (ROS 17/2.8). Moreover, E2 failed to stimulate DNA synthesis in vitamin D-depleted female rat bone in the absence of prior i.p. injections of 1.25(OH)2D3. We have, therefore, studied the effects of pretreatment of cells by one hormone on their response to challenge by a second hormone. We now report reciprocal interactions of sex steroids and other hormones modulating bone formation on cell proliferation parameters in primary bone and cartilage cell cultures: these interactions can selectively augment or diminish cell responsiveness to a given hormone. Pretreatment of rat epiphyseal cartilage cell cultures with 1.25(OH)2D3, 24.25(OH)2D3 or parathyroid hormone (PTH) for 5 days, followed by E2 treatment for 24h, resulted in increased DNA synthesis compared to cultures pretreated with vehicle. Prostaglandin (PGE2) pretreatment blocked further response to E2. In the reciprocal case, rat epiphyseal cartilage cells, pretreated with E2, showed an increased response to PTH, a loss of the response to PGE2 or 24.25(OH)2D3 and an inhibition of CK activity and DNA synthesis by 1.25(OH)2D3, similar to the characteristic inhibitory action of 1.25(OH)2D3 in osteoblasts. By contrast, rat epiphyseal cartilage cells pretreated with testosterone showed no changes in response to PTH, 24.25(OH)2D3 or PGE2 and a decreased response to E2, but were stimulated by 1.25(OH)2D3. Rat embryo calvaria cell cultures behaved similarly to epiphyseal cartilage cultures except that 24.25(OH)2D3 pretreatment did not increase the response to E2. Reciprocally, pretreatment with E2 before exposure to calciotrophic hormones did not change the responses of rat embryo calvaria cell cultures to 1.25(OH)2D3 or 24.25(OH)2D3. These findings suggest that the mutual interactions between calciotrophic hormones and E2, demonstrated here in vitro, could selectively affect the responses of bone and cartilage cells to E2 by several mechanisms. These possibilities include increased E2 receptors and E2-stimulated differentiation of cartilage cells to more E2 responsive cells showing some characteristics of osteoblasts.

24,25-Dihydroxyvitamin D 3↗
PubMed1990

Hormonal stimulation of bone cell proliferation.

The recent demonstration of estrogen receptors in bone derived cells has stimulated the study of direct effects of sex steroids on bone. We have shown direct stimulation of proliferation by 17 beta-estradiol (E2) of ROS 17/2.8 rat osteogenic osteosarcoma cells, and other bone-derived cells in culture, as well as sex-specific stimulation of diaphyseal bone in vivo by estrogen and testosterone, using [3H]thymidine incorporation into DNA and stimulation of the specific activity of creatine kinase as markers. ROS 17/2.8 cells were used as models of osteoblast-like cells to study the reciprocal modulation of stimulation of bone cell proliferation by sequential treatment by sex steroid and calciotrophic hormones. Pretreatment with 1,25(OH)2D3 and PTH augmented stimulation by E2, while pretreatment with PGE2 followed by E2 resulted in no additional stimulation. Reciprocally, pretreatment with E2 significantly reduced the response to PGE2 while showing an insignificant effect on the response to the other hormones. Gonadectomized Wistar-derived rats provided a useful model system for study of postmenopausal osteoporosis. In diaphyseal bone, [3H]thymidine incorporation and creatine kinase activity decreased 4 weeks after gonadectomy. At that time, a single i.p. injection of E2 in females, and testosterone in males, resulted in a highly significant increase in both these parameters within 24 h.

Animals↗
PubMed1990

Prenatal diagnosis of vitamin D-dependent rickets, type II: response to 1,25-dihydroxyvitamin D in amniotic fluid cells and fetal tissues.

Vitamin D-dependent rickets type II (VDDR-II; hereditary resistance to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]), an autosomal recessive genetic disease that results from a failure to respond to 1,25-(OH)2D3, is characterized by severe rickets, hypocalcemia, growth retardation, and high prevalence of alopecia. We used amniotic fluid cells in the 17th week of gestation to detect VDDR-II in fetuses at risk for the defect. First, we demonstrated in cells obtained from 15 control pregnancies the presence of a specific high affinity 1,25-(OH)2D3 receptor (Kd = 0.3 x 10(-11) mol/L; maximal number of binding sites, 6.1 fmol/mg protein) and 1,25-(OH)2D3-induced 25-hydroxyvitamin D3-24-hydroxylase activity (up to 30-fold increase). Amniotic fluid cells from a woman who had already given birth to a child with VDDR-II contained receptors that bound [3H]1,25-(OH)2D3 normally and responded to 1,25-(OH)2D3 stimulation with a 10-fold increase in 24-hydroxylase activity. The fetus was, therefore, judged unaffected, and a normal baby girl was born. At the age of 16 months she did not demonstrate clinical or biochemical features of VDDR-II. Amniotic fluid cells from another mother of a child with VDDR-II were unable to bind [3H]1,25-(OH)2D3, and the hormone failed to stimulate 24-hydroxylase activity. VDDR-II in this fetus was confirmed after termination of pregnancy by the total inability of 1,25-(OH)2D3 to stimulate 24-hydroxylase activity in tissue explants and cell cultures prepared from the fetus's kidney and skin. In contrast, tissues from dead control fetuses responded to stimulation by 1,25-(OH)2D3 with a 3- to 10-fold increase in 24-hydroxylase activity. Fetal kidney and skin explants and cell cultures also synthesized a [3H]1,25-(OH)2D3-like metabolite from [3H]25-OHD3 as early as the 17th week of gestation. 1,25-(OH)2D3 (10 nM) decreased the in vitro synthesis of the [3H]1,25-(OH)2D3-like metabolite in tissues from dead control fetuses, but not from the affected fetus. Thus, human fetuses at midgestation already have the regulatory mechanisms responsive to 1,25-(OH)2D3 present postnatally. The prenatal diagnosis of VDDR-II is now possible and is indicated in a high risk family.

Adult↗
PubMed1989

Estradiol induction of accelerated energy metabolism in prepuberal rat uteri in vitro: mRNA hybridization and [13C]NMR studies.

In vitro treatment with 30 nM 17 beta-estradiol stimulated the induction of mRNA for the brain type isozyme of creatine kinase BB (CKBB) and stimulated glucose metabolism in perifused uteri from 27-29-day-old rats. The perifusion conditions maintained the normal NMR spectrum of high energy phosphates for at least 24 h. This technique permitted the demonstration that perifused rat uteri stimulated by 17 beta-estradiol show increased mRNA for creatine kinase BB, 1 h after estrogen addition. The time-course of increase, measured by Northern blot hybridization, parallels that seen in mRNA extracted from uteri after in vivo induction by i.p. injection of 5 micrograms 17 beta-estradiol; the maximal increase is seen at 2-4 h. Experiments utilizing actinomycin D (4 micrograms/ml) for inhibition of RNA synthesis showed that CKB mRNA from both untreated and estradiol stimulated uteri had a similar half-life, of approximately 2 h, indicating that CKB mRNA is transcriptionally regulated. In the same system, the rate of glycolysis was measured by NMR spectroscopy using [1-13C]glucose. Following in vitro stimulation with 30 nM estradiol, glycolysis increased within 3 h, in parallel to increases previously found in uteri from in vivo stimulated rats.

Animals↗
PubMed1989

Direct and sex-specific stimulation by sex steroids of creatine kinase activity and DNA synthesis in rat bone.

A direct in vitro effect of 17 beta-estradiol (E2) was demonstrated on bone and cartilage cell energy metabolism. Sex-specific stimulation by E2 and testosterone was shown in diaphyseal bone of weanling rats. E2 (30 nM) caused, within 24 hr, a 70-200% increase in creatine kinase (CK; ATP:creatine N-phosphotransferase, EC 2.7.3.2) specific activity in ROS 17/2.8 rat osteogenic sarcoma cells, MC3T3-E1 mouse calvaria-derived cells, and rat fetal calvaria cells, and a 40% increase in rat epiphyseal cartilage cells. Stimulation of CK activity by E2 was dose and time dependent: in ROS 17/2.8 cells, a highly significant increase was found at 3 nM E2 and a greater than 100% increase in CK activity was found 1 hr after E2 administration. In female 20-day-old Wistar-derived rats, E2 (5 micrograms per rat) increased CK activity in diaphyseal bone by 82% within 1 hr of i.p. injection, with a maximal increase of 200% after 24 hr; neither the weakly estrogenic agonist 17 alpha-estradiol, testosterone, nor progesterone showed this effect. Conversely, in male rat diaphyseal bone, testosterone or dihydrotestosterone increased CK activity after 24 hr by approximately 100%, while E2 was ineffective. In epiphyseal cartilage, both E2 and testosterone increased CK activity. Stimulation of CK activity by sex hormones was paralleled by significant increases in [3H]thymidine incorporation into DNA. Therefore, it is possible that direct sex-specific actions of gonadal steroids may contribute to stimulating bone growth and maintaining balanced bone turnover.

Animals↗
PubMed1989

Modulation by vitamin D status of the responsiveness of rat bone to gonadal steroids.

We have previously demonstrated that gonadal steroids stimulate [3H]thymidine incorporation and creatine kinase specific activity in skeletal tissues. In the present study we report that in 20-day-old vitamin D-deficient Wistar-derived rats, 17 beta-estradiol (E2; 5 micrograms/rat) or testosterone (50 micrograms/rat) failed to stimulate [3H]thymidine incorporation into diaphyses of long bones and that the response to these hormones in terms of increased creatine kinase specific activity was less than half the value in normally fed rats. Two daily ip injections of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3; 0.5 ng/g BW], but not 24,25-(OH)2D3 (5 ng/g BW), partially restored the biological responses to E2 in bone of 21-day-old vitamin D-deficient female rats. Vitamin D deficiency did not impair the responsiveness to gonadal steroids in the epiphysis of long bones, uterus, or prostate, in contrast to its effect on diaphysis. In 21-day-old normally fed female rats, neither vitamin D metabolite enhanced the response to E2. When cultures of rat epiphyseal cells were treated daily for 5 days with either 1,25-(OH)2D3 (1 nM) or 24,25-(OH)2D3 (10 nM), followed by E2 (30 nM) for 24 h, creatine kinase activity was significantly higher than in cultures treated daily for 5 days with vehicle alone, and then with E2. The same treatment of rat embryo calvaria bone cells showed that 1,25-(OH)2D3, but not 24,25-(OH)2D3, significantly increased the creatine kinase activity response to E2. These findings suggest that vitamin D metabolites selectively affect the biological responses of skeletal tissues to gonadal steroids.

Animals↗
PubMed1988

Acute stimulation of creatine kinase activity by vitamin D metabolites in the developing cerebellum.

There is increasing evidence that vitamin D metabolites have a developmental function. We have investigated the influence of the vitamin D status on the activity of creatine kinase in the brain. Normally fed rats show an increase in the specific activity of cerebral and cerebellar creatine kinase during postnatal development. Vitamin-D-depleted rats failed to show this normal increase. Developing cerebellum, but not cerebrum, in both vitamin D-depleted rats and in normally fed animals, responded sequentially to a single injection of a vitamin D metabolite by displaying increased creatine kinase specific activity. In 5-25-day-old rats, 24R,25-dihydroxyvitamin D-3 significantly increased creatine kinase specific activity 24 h after injection. In contrast, 1,25-dihydroxyvitamin D-3 stimulated cerebellar creatine kinase activity from 20 days after birth. A similar pattern of sequential responsiveness to vitamin D metabolites, but at an earlier age, was shown in the cerebellum of the rabbit, which is a 'perinatal brain developer' compared to the rat, a 'postnatal brain developer'. Because of the difficulty in obtaining vitamin D-depleted rabbits, studies were carried out in normally fed animals. In these rabbits, 24R,25-dihydroxyvitamin D-3 stimulated cerebellar creatine kinase activity between 6 days before birth and 9 days after birth, while 1,25-dihydroxyvitamin D-3 caused an increase in cerebellar creatine kinase specific activity from 8 days after birth. These developmental differences found in creatine kinase basal activity and responsiveness are correlated with differences in cellular growth rates, both in the rabbit and in the rat, suggesting that vitamin D metabolites may be required for optimal cerebellar development.

Age Factors↗
PubMed1988

The transduction of mechanical force into biochemical events in bone cells may involve activation of phospholipase A2.

Mechanical forces applied to cultured bone cells induce the production of cAMP via stimulation of the formation of prostaglandin E2 (PGE2) and its release into the medium, resulting in stimulation of adenylate cyclase. In this paper we show that either the antibiotic gentamycin (100 micrograms/ml) or antiphospholipid antibodies (0.1%) which bind to membrane phospholipids abolish cAMP formation induced by mechanical forces; exogenously added arachidonic acid or PGE2 stimulates cAMP formation, even in the presence of these agents. Addition of exogenous phospholipase A2 (but not phospholipase C) causes an increase in the formation of cAMP in bone cells, a response that is also inhibited by gentamycin or antiphospholipase antibodies. These observations suggest that mechanical forces exert their effect on bone cells via the following chain of events: (1) activation of phospholipase A2, (2) release of arachidonic acid, (3) increased PGE synthesis, (4) augmented cAMP production.

Animals↗
PubMed1988

Vascular placental insufficiency in the rabbit. Changes in creatine kinase and adenylate kinase activities in fetal tissues.

Vascular placental insufficiency is considered a common pathogenic factor in human intrauterine growth retardation. To mimic this condition, the rabbit, a 'perinatal brain developer' was utilized as an experimental model. Ischemic conditions were achieved by total ligation of approximately 30% of the uteroplacental vessels of half of the fetuses in each pregnant rabbit in the last third of gestation. The change in activity of the brain type isozyme of creatine kinase (CKBB), involved in energy regeneration and regulation, was assessed as a response marker to tissue ischemia in rabbit tissues: cerebellum, cerebrum, kidney, liver and placenta. A significant transient increase in CK-specific activity was found in the kidney and the cerebellum but not in the other organs tested, at 24 and 48 h after ligation. This increase was not seen with adenylate kinase, another enzyme involved in energy regeneration and regulation. It is proposed that an increase in CK-specific activity could serve as a metabolic marker of vascular insufficiency in rapidly developing tissues, representing part of a compensatory mechanism to overcome an energetic gap induced by ischemia.

Adenylate Kinase↗
PubMed1988

Effects of 17 beta-estradiol on high energy phosphate concentrations and the flux catalyzed by creatine kinase in immature rat uteri: 31P nuclear magnetic resonance studies.

31P nuclear magnetic resonance (NMR) was used to study the effects of 17 beta-estradiol on the content of phosphates and on the flux catalyzed by creatine kinase in immature rat uteri. Perifusion with oxygenated medium at 36 C maintained the uteri in a viable state for at least 10 h in vitro during 31P NMR measurements. In vitro administration of 17 beta-estradiol to the perifused uteri induced changes in the concentration of the high energy phosphates similar to those found after in vivo stimulation: a rapid fall in the concentrations of ATP, phospho-creatine, and the phosphomonoesters during the first 2 h, followed by a slower return to initial concentrations by approximately 6 h. Analysis of the time course of this modulation indicated that after estrogen stimulation, the energy utilization rate was about twice the production rate. The flux through the creatine kinase (CK) reaction was measured independently using 31P magnetization transfer techniques; it was found to increase in uteri 24 h after estradiol injection by the same extent (65%) as the specific activity of CK measured by a spectrophotometric assay. The congruence between the results of these two techniques (in the absence of increased substrate concentrations) provides evidence that the early stimulation of brain-type CK synthesis by estrogen results in a net increase in the concentration of this enzyme.

Algorithms↗
PubMed1988

Prolactin stimulates creatine kinase activity and DNA synthesis in explants of human amnion.

To characterize the action of hPRL and human placental lactogen on the amnion, decidua and placenta, we examined the effects of these hormones on the brain type isozyme of creatine kinase in cultured explants of these tissues from normal deliveries. In the amnion, hPRL (1 mg/l) caused a 1.8-fold increase in creatine kinase specific activity in 24 h, whereas hGH (1 mg/l) or human placental lactogen (1 mg/l) had no effect; oPRL (1 mg/l) also caused a 2.5-fold increase in creatine kinase activity. Neither hPRL, human placental lactogen nor hGH had a significant effect on creatine kinase activity in the placenta or decidua. [3H]thymidine incorporation into DNA increased in parallel to the stimulation of creatine kinase activity. The predominant isozyme of creatine kinase in both the unstimulated and stimulated explants was the brain type isozyme. Creatine kinase activity in the amniotic tissue increased significantly 2 h after hPRL treatment and reached its highest value at 4 h. The enzyme activity in the amnion rose with increasing hPRL dose and showed a significant increase at physiologic concentrations as low as 0.01 mg/l. This study, therefore, provides evidence for biological action of prolactin in amniotic tissue, suggesting that the amnion is physiologically responsive to prolactin.

Amnion↗