摘要:

Thein vitrobioactivity of the humanβTSH subunit was investigated utilizing eleven overlapping synthetic peptides representing the entire 112 residue sequence. The peptides were tested for both stimulatory and inhibitory activity in two sensitive bioassay systems: the first based on cAMP production in FRTL-5 rat thyroid cells, and the second based on stimulation of iodine trapping by the same continuous cell line. Peptides from three distinct regions of theβ-subunit showed concentration dependent inhibition of TSH bio-activity, includingβ1–15,β11–25,β31–45,β81–95, andβ91–105 with IC50values ranging from 150 to 304μM. An additional peptide representing the entire sequence of the“intercysteine loop”region ofβTSH,β31–52, also inhibited TSH activity With somewhat higher potency than its fragment peptideβ31–45 (IC50of 87.5±14.7μM forβ31–52 versus 207±92.4μM forβ31–45). Three of these,β1–15,β31–45, andβ31–52, also inhibited binding of TSH to the receptor in a radio-receptor assay, as previously reported (1), supporting their importance in receptor interaction. None of the synthetic peptides stimulated either cAMP production or iodine trapping. Two other overlapping peptides,β81–95 andβ91–105, possessed bio-inhibitory activity but did not inhibit binding of labeled TSH. Computer analysis of this sequence predicted an extended turn structure for this region. This region has been referred to as the“determinant loop”as it is bounded by cysteine residues at positions 88 and 95 that many believe form a disulfide bond in the native subunit. The current data suggests theβ88–95 region may play a role in receptor activation after initial binding of hormone to receptor.

ISSN:0743-5800    

DOI:10.1080/07435809209035924

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Daily subcutaneous injections of rat derived growth hormone to immature, hypophysectomized rats stimulated significant increases in body weight gain, serum osteocalcin, skeletal alkaline phosphatase and incorporation of radioactive thymidine and proline into the compact bone of femurs and tibiae. Equimolar doses of insulin-like growth factor-II did not produce similar biological effects. The data support the contention that is insulin-like growth factor-II in vivo.

ISSN:0743-5800    

DOI:10.1080/07435809209035925

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Pertussis toxin (PT) and cholera toxin (CT) have been shown to modulate lactogenic hormone-stimulated Nb2 cell mitogenesis, a lactogen-dependent cell line. As both toxins have been shown to alter guanylate cyclase activity in other cell systems, cyclic guanosine monophosphate (cGMP) analogs, 8-bromo or dibutyryl cGMP, were added to determine if they could reverse the toxin-mediated effects. In the absence of bacterial toxins, both cGMP analogs enhanced lactogen-stimulated Nb2 cell mitogenesis in a multiphasic pattern. At maximal enhancement, the effect was statistically significant but not marked (113±5%; p<0.01). Neither cGMP analog increased lactogenic binding site number or affinity so cGMP must affect lactogen action following receptor binding. Neither analog could stimulation Nb2 cell mitogenesis in the absence of lactogens so cGMP is not a second messenger for lactogens in this cell system. Finally, neither cGMP analog reversed the inhibitory effects of either bacterial toxin on lactogen-stimulated Nb2 cell proliferation. In summary, although bacterial toxins may be capable of altering guanylate cyclase activity, as addition of cGMP analogs do not reverse toxin-mediated effects on lactogen-stimulated mitogenesis, these toxins' actions must be mediated predominantly through other mechanisms that may have significant importance to lactogen signal transduction.

ISSN:0743-5800    

DOI:10.3109/07435809209035926

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Endogenous opioids are thought to participate in the regulation of growth hormone (GH) release through the mediation of growth hormone releasing hormone (GHRH). This study was intended to investigate whether the endogenous opioid beta-endorphin could modulate the GH response to GHRH and if this hypothesis could be demonstrated in children with familial short stature with or without constitutional growth delay.Seventeen children (6 female and 11 male) with stature below the fifth percentile were studied to rule out disorders in growth hormone dynamics. All had normal growth velocities, had appropriate predicted heights for their families and had normal GH levels on standard testing. Eight were prepubertal and 9 were Tanner II.All were given 0.1 mcgm/kg (1–44)hpGHRH-NH2IV. Blood for growth hormone was obtained at 0,15,30,45,60,90 and 120 minutes. Blood for beta-endorphin and cortisol was obtained at 0 and 60 minutes. The basal beta-endorphin level significantly correlated with the peak GH level (r=0.868, p<0.05) in the prepubertal group only. In the same group of children, the degree of the negative feedback on the beta-endorphin level correlated significantly with the rise in GH level (r=0.912, p<0.01). However, there was no correlation between the basal beta-endorphin and the peak GH level nor between the rise in GH level and the change in beta-endorphin in the pubertal children. These data are compatible with the hypothesis that beta-endorphin levels affect the GH response to GHRH in prepubertal children, but have no discernible effect on the GH response to GHRH in pubertal children.

ISSN:0743-5800    

DOI:10.1080/07435809209035927

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Exposed sites onPseudomonas maltophilia(ATC #1637), which bind both human chorionic gonadotropin (hCG) and a native hCG-like ligand with equal high affinity, are described. This high-affinity binding site (Kd = 1.3 X 10-10) binds hCG, but does not bind human luteinizing hormone (hLH), nor related human glycoprotein hormones, thyrotropin, and follicle stimulating hormone. A lower affinity, 2.3 X 10-9, is also described which binds hLH and hCG equally well. This is the first description of a high-affinity binding site in nature, which distinguishes hCG from hLH.

ISSN:0743-5800    

DOI:10.3109/07435809209035928

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

This study investigates the effect of pertubation of the normal pituitary-adrenal axis on concentrations of adrenocorticotropin (ACTH)-like immunoactivity in peripheral tissues. We used a polyclonal antibody (West antibody) to measure ACTH-like immunoactivity in glacial acetic acid extracts of five tissues in adult male rats at increasing times (1, 7, 14, and 28 days) after hypophysectomy or adrenalectomy, and in normal control rats.Concentrations of ACTH-like immunoactivity were similar to those previously reported in liver, colon, heart, and small intestine and were not significantly affected by either hypophysectomy or adrenalectomy. While hypophysectomy also had no effect in the kidney, adrenalectomy resulted in a four-fold increase in extractable immunoactivity, first noticeable at seven days (p<0.005), but increasing progressively to 28 days (p<0.0005). Gel filtration showed that most of the increase in activity in kidneys of adrenalectomized rats corresponded to the 4.5 kD form comprising most of the serum ACTH immunoactivity and suggesting that the activity increase in kidney was largely due to ACTH derived from blood.

ISSN:0743-5800    

DOI:10.1080/07435809209035929

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

We report preliminary data on the standardization of a device used in the recently developed“Oral Diffusion Sink”(ODS) technology for the timeintegrated measurement of salivary corticosteroids. The concentrations of corticosteroids collected with the ODS devices were compared to plasma cortisol and saliva corticosteroid levels measured simultaneously.Six volunteers installed the ODS devices into their mouths during unstimulated and ACTH (250μ) stimulated periods. Blood and saliva samples were also collected during these periods. The integrated plasma cortisol response and saliva corticosteroid levels were strongly correlated with the time-integrated total corticosteroid measurement of the ODS devices as well as with the cortisol and cortisone fractions.This preliminary data suggests that the accuracy of assessing adrenocortical activity by the measurement of salivary corticosteroids collected with the ODS device is high in both normal and stimulated conditions in normal volunteers. Continued standardization and studies in the practical use of this technology could lead to an important tool in assessing adrenocortical abnormalities. The use of such technology would increase the convenience while reducing the cost and invasiveness of current provocative testing of adrenal functioning.

ISSN:0743-5800    

DOI:10.1080/07435809209035930

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor