Second messengers, steroids and signaling cascades: Crosstalk in sperm development and function.

Signaling cascades control numerous aspects of sperm physiology, ranging from creation to fertilization. Novel aspects of several kinases and their influence on sperm development will be discussed in the first section and cover proliferation, chromatin remodeling and morphology. In the second section, protein kinases (A, B and C) that affect sperm function and their regulation by second messengers, cyclic-AMP and phosphoinositides, as well as steroids will be featured. Key areas of integration will be presented on the topics of sperm motility, capacitation, acrosome reaction and fertilization.

Measurement of leptin and insulin-like growth factor-I in seminal plasma from different species.

The multi-functional proteins, insulin-like growth factor-I (IGF-I) and leptin were present in seminal plasma from different species. Concentrations of IGF-I in equine and porcine semen were 20 and 17.5 ng/ml, respectively. Seminal plasma concentrations of leptin were 1 ng/ml in human and 11 ng/ml in porcine samples.

Residues from anabolic preparations after good veterinary practice.

The purpose of this study was to determine the endogenous concentrations of estrogens, particularly estradiol-17beta (E2beta, in edible tissues of beef cattle (females and intact and neutered males) and the concentrations of E2beta, and trenbolone beta and alpha (betaTb, alphaTb) after an E2beta and/or trenbolone acetate (TA) ear implant. Radioimmunoassays were validated for quantitation of E2beta (active isomer), E2alpha, estrone (E1), betaTb and alphaTb for bovine muscle, liver, kidney and fat tissues. The criteria of accuracy, precision, specificity and sensitivity were applied according to the standards of the U.S. Food & Drug Administration. In steer tissues, endogenous E2beta was <15 ppt, as was heifer muscle; but heifer liver and kidney were 3-fold greater. An E2beta implant in steers had no effect on muscle E2beta concentration, but increased E2beta in liver and fat 4- and 3-fold, respectively, but by 24 h post-implant removal, E2beta had fallen by half. Tissue E1 concentrations in cyclic females were similar to E2beta, but rose many fold greater than did E2beta during gestation; E2beta rose 3-fold during gestation. After E2beta/TA implant, steer tissues had E2beta concentrations equal to (for muscle and fat) and one-half (for liver) the E2beta measured in E2beta implant only steers; betaTb was in a low range (250-380 ppt) in muscle, liver and fat and alphaTb was even lower, except in liver (800-1500 ppt). An implant of TA only (no E2beta) resulted in betaTb and alphaTb concentrations 2-3-fold greater in liver, kidney and fat, but no greater in muscle than betaTb in tissues of E2beta/TA implant steers. In conclusion, anabolic implants in steers resulted in tissue E2beta concentrations less than the FDA allowable increment and betaTb in the lowest quartile (0.25) of a part per billion 30 days after implant.

Crosstalk and considerations in endocrine disruptor research.

The presence of endocrine disrupting chemicals in the environment has prompted action on several fronts to assess the potential health risks of these compounds. To fully understand the mechanisms behind the observed endocrine disruption, crosstalk and other factors should be considered. In this article we will discuss how crosstalk modulates estrogen action in several common assays and how this and other considerations appear to have been overlooked. In addition, a paradigm shift from theoretical linear response pathways to interaction maps should aid in the understanding and analysis of endocrine disruption.

Synergistic approach to cancer therapy: exploiting interactions between anti-estrogens, retinoids, monoterpenes and tyrosine kinase inhibitors.

Non-responsiveness and toxicity are large problems encountered during cancer treatment. Utilization of compounds that synergize should increase treatment efficacy while avoiding problems of toxicity. This review explores interactions between classes of compounds, including anti-estrogens, retinoids, monoterpenes and tyrosine kinase inhibitors, that are effective independent, and how their synergistic interaction could be exploited in cancer treatment. The effects of these compounds on insulin-like growth factors (IGF) and transforming-growth factor-beta (TGF-beta) will also be examined.

Physiological basis for use of insulin-like growth factors in reproductive applications: a review.

The insulin-like growth factors (IGF-I and -II) are ubiquitously expressed factors that regulate cell growth, differentiation and maintenance of differentiated cell function. All aspects of male and female reproduction are influenced by the IGF system. This review will examine the IGF system as it pertains to reproductive physiology and applications.

Does the insulin-like growth factor system interact with prostaglandins and proinflammatory cytokines during neurodegeneration?

Prostaglandins and proinflammatory cytokines are implicated in the etiology of neurodegenerative diseases, such as Alzheimer's disease. Signaling cascades initiated by these factors may result in reactive oxygen species generation and cell death. The insulin-like growth factors (IGF) are ubiquitous polypeptides involved in all aspects of growth and development. Additionally, the IGF are regarded as survival factors that display potent antiapoptotic activity. Interfering with IGF production, distribution, or signaling may result in greater susceptibility to apoptotic stimuli. In neurodegenerative conditions, the IGF appear to be antagonized by prostaglandins and proinflammatory cytokines. In this review, the relationship among specific prostaglandins, the proinflammatory factors, tumor necrosis factor, interleukin-1, and interleukin-6, and the IGF system will be investigated.

Actions and interactions of the IGF system in Alzheimer's disease: review and hypotheses.

Insulin-like growth factors (IGF) are pleiotrophic polypeptides affecting all aspects of growth and development. The IGF system, including ligands, receptors, binding proteins and proteases is also involved in pathophysiological conditions, such as cancer and degenerative conditions. In this review, the actions and interactions of the IGF system as it relates to Alzheimer's disease will be investigated.

The insulin-like growth factor (IGF) system and gonadotropin regulation: actions and interactions.

Insulin-like growth factors (IGF) are polypeptides that regulate growth, differentiation and survival in a multitude of cells and tissues. The IGF system consists of ligands, receptors, binding proteins and binding protein proteases. The influence of the IGF system on reproductive parameters, specifically gonadotropin release and interactions between the IGF system and other effectors of gonadotropin release will be examined in this review.

Computer-assisted sperm motion analysis of bovine sperm treated with insulin-like growth factor I and II: implications as motility regulators and chemokinetic factors.

The effects of insulin-like growth factors (IGFs) I and II on motility of bovine sperm were examined using a computer-assisted sperm motion analyzer (CASA). The following kinematic parameters were examined: percentage of rapidly moving cells, straight-line velocity , curvilinear velocity, average path velocity, amplitude of lateral head displacement, and beat cross frequency. Sperm were treated with IGF-I (100 ng/mL) or IGF-II (250 ng/mL) and compared to sperm in modified Tyrodes' medium only (control) at 90, 180, and 360 min using CASA. Insulin-like growth factor I and II increased the percentage of rapidly moving cells, straight-line velocity, curvilinear velocity, average path velocity, amplitude of lateral head displacement, and beat cross frequency compared to the control treatment. These results indicate that IGFs may be involved in initiation and maintenance of bovine sperm motility.

Identification of insulin-like growth factor I in bovine seminal plasma and its receptor on spermatozoa: influence on sperm motility.

Insulin-like growth factor I (IGF-I) has been identified in human seminal plasma. This study was conducted to determine whether IGF-I is present in bovine seminal plasma, whether sperm cells express the IGF-I receptor (IGF-IR), and whether IGF-I affects sperm motility. Semen samples were collected from bulls by electroejaculation and maintained at 37 degrees C, and motility of sperm was assessed. After centrifugation to separate sperm cells from seminal plasma, the seminal plasma was submitted to a validated heterologous RIA for IGF-I. Significant concentrations of IGF-I (116.29 +/- 40.83 ng/ml expressed as mean +/- SD) were measured in bovine seminal plasma. Sperm cells were washed with buffer and subjected to either radioreceptor assay (RRA) or immunocytochemistry (IC). RRA revealed a single high affinity for the IGF-IR with a Kd of 0.83 nM as determined by the computer program LIGAND. IC, using three monoclonal antibodies, localized the IGF-IR to the acrosomal region of the sperm. Computer-assisted sperm-motion analysis was used to determine the effects of IGF-I and IGF-II on bovine sperm motility parameters. Both IGF-I and IGF-II increased sperm motility and straight-line velocity (p < 0.05) relative to the control. The presence of IGF-IR on sperm, the presence of IGF-I in semen, and the ability of IGF-I to stimulate sperm motility provide evidence that the IGF system may be involved in the fertilization process in the bovine species.

The adenosine 5',5"',P1,P4-tetraphosphate receptor is at the cell surface of heart cells.

We have previously demonstrated the existence of an adenosine 5',5"',P1,P4-tetraphosphate (Ap4A) receptor in mouse hart membrane fractions [Hilderman, R. H., Martin, M., Zimmerman, J. K., & Pivorun, E. P. (1991) J. Biol. Chem. 266, 6915-6918]. However, we did not determine the cellular localization or distribution of the receptor. In this report, the Ap4A receptor is shown to be on the cell surface of individual mouse heart cells by the following four methods: (1) intact cells show specific, saturable, and reversible binding of Ap4A; (2) monoclonal antibodies (Mabs) raised against the Ap4A receptor inhibit Ap4A binding to its receptor on intact heart cells; (3) bound Mabs are shown to be at the outer cell surface via reaction with a alkaline phosphatase conjugated goat anti-rat IgG; (4) when intact cells are labeled with the impermeable cell surface labeling reagent, (sulfosuccinimido) biotin, labeled receptor is immunoprecipitated with Mabs. Furthermore, subcellular fractionation of mouse hearts demonstrates that virtually all of the Ap4A receptor is associated with a membrane fraction with at least 77% of the active receptor on plasma membranes.