Hormones are the chemical messengers of the body they are secreted by the endocrine glands and regulate biological processes Corticosteroids described m the preceding sec tion are hormones produced by the adrenal glands The sex glands—testes m males ovaries m females—secrete a number of hormones that are involved m sexual develop ment and reproduction Testosterone is the principal male sex hormone it is an androgen  [c.1098]

Testosterone and estradiol are present m the body m only minute amounts and their isolation and identification required heroic efforts In order to obtain 0 012 g of estradiol for study for example 4 tons of sow ovaries had to be extracted  [c.1100]

Chinese hamster ovary cells  [c.192]

Toxicology and Safety. Because of their strong acidity, the perfluorinated carboxyflc acids themselves are corrosive to the skin and eyes. Protective clothing, ie, gloves and face shield/safety glasses, should be employed when handling them (48,49). Although perfluorooctanoic acid has been found to be corrosive to the eyes and severely irritating to the skin on contact, it is only slightly toxic on oral contact. The acute LD q (rat) of perfluorooctanoic acid was found to be slightly less than 1000 mg per kg of body weight. However, in feeding studies the test animals suffered erosion of the gastric mucous membrane because of corrosivity of the acid (50). Perfluorodecanoic acid has been assessed for its genotoxic activity. It was found to test negative in the Ames test, Chinese hamster ovary gene mutation assay, sister chromatid exchange assay, chromosomal aberration assay, and m vivo]in vitro unscheduled DNA synthesis. Chromosomal aberrations were observed only when the S-9 fraction was incubated with perfluorodecanoic acid in the S-phase DNA synthesis assay (51).  [c.312]

Steroids are synthetic products of cholesterol [57-88-5]. The chemical stmcture of a steroid hormone is determined by sequential enzymatic processing of the cholesterol molecule. Steroid products differ among steroid-secreting glands because of differences in enzyme processing, eg, the production of estrogen by the ovary requires enzymatic steps that do not occur in the adrenal cortex.  [c.171]

There are three pituitary glycoprotein hormones, ie, luteinizing hormone (LH), follicle-stimulating hormone (ESH), and thyroid-stimulating hormone (TSH). Luteinizing hormone and ESH control significant aspects of reproduction. These hormones are referred to as gonadotropins, owing to thek trophic and stimulatory effects on gonadal tissues. Follicle-stimulating hormone is needed for maturation of the ovarian foUicles, for maintaining the size of the ovary, and for stimulating the production of female sex steroid hormones, ie, estrogens. In the male, FSH is necessary for sperm production. Luteinizing hormone induces ovulation, ie, release of the egg, from the mature foUicle. In the male, LH induces the synthesis of the male sex steroid hormones, called androgens (see Hormones, sex hormones). Thyroid-stimulating hormone is necessary for the proper development, growth, and function of the thyroid gland. Most importantiy, TSH is responsible for maintaining thyroid hormone production. Inadequate levels of thyroid hormone give rise to a clinical profile characterized by sluggish mental processes, slow growth, sensitivity to cold, low basal metaboHc rate, cardiac insufficiency, general weakness, and susceptibihty to infection.  [c.176]

Turner s Syndrome. Turner s syndrome is a genetic disorder of females characterized by short stature, nonfunctioning ovaries, and failure to develop secondary sexual characteristics. Several clinical trials in the United States, Europe, and Japan have demonstrated that hGH can accelerate  [c.196]

Effects of Progestins on Various Target Tissues. Progestins exert a variety of direct and indirect effects on all tissues and organs within the reproductive system. Organs that contain progestin receptors, and thus can respond direcdy to progestins, include the utems, cervix, vagina, breast, ovary, brain, and pituitary gland (258,259). Receptors have also been identified in rat thymus (260), human lymphocytes (261), and bone cells (262,263). Several factors are responsible for progestin effects including the dose and potency of the dmg itself, the duration of treatment, the route of adrninistration, and the ability of the dmg to affect progestin-receptor number and estrogen levels.  [c.222]

Estrogens stimulate cellular proliferation, induce RNA and protein synthesis of uterine endometrium and the fibrous connective tissue framework for ovaries, and increase the size of the cells. This effect leads to the growth and regeneration of the endometrial layer and spinal arterioles, and increase in the number and size of endometrial glands. Under the influence of estrogen, vaginal mucosa becomes thicker, as cervical mucus becomes thinner (85,86).  [c.242]

Many biological systems exhibit the properties of Hquid crystals. Considerable concentrations of Hquid crystalline compounds have been found in many parts of the body, often as sterol or Hpid derivatives. A Hquid crystal phase has been impHcated in at least two degenerative diseases, atherosclerosis and sickle ceU anemia. Living tissue, such as muscle, tendon, ovary, adrenal cortex, and nerve, show the optical birefringence properties that are characteristic of Hquid crystals. The Hquid crystal state has been identified in many pathological tissues, particularly in areas of large Hpid deposits. Massive deposits of Hquid crystalline cholesterol derivatives have been found in the kidneys, Hver, brain, spleen, marrow, and aorta walls. Certain living sperms possess a Hquid crystalline state. Solutions of tobacco mosaic vims (TMV), coUagen, hemoglobin of sickle ceU anemia, native protein, nucleic acid genetic material, and fibrinogen also show resemblances to the Hquid crystal state.  [c.202]

Procedure Thyroid Marrow Breast Lung Ovaries  [c.51]

Several organic peroxides have been tested for mutagenicity in bacterial and animal cells, and in animals. In general, a variety of short-term screening studies have indicated that many organic peroxides are mutagenic when tested in bacterial and animal cells, but are not mutagenic when tested in whole animal studies. Eor example, tert-huty hydroperoxide was mutagenic in the Ames test in mouse lymphoma assay, and produced chromosomal damage in Chinese hamster ovary cells, but did not demonstrate mutagenic activity in rat bone marrow after inhalation exposure for five days, and in a mouse dominant lethal study (274). Similar findings have been reported with MEKPs and tert-huty peroxybenzoate (277,278).  [c.132]

Endocrine System Disruption. The dismption of the endocrine system by certain substances mimicking or blocking the effects of estrogen, a hormone generated by the ovaries, testes, and adrenal that plays many roles in the body, such as ovulation, blood clotting, bone growth, and modulating the immune system, is still another toxic response (36—39). In the fetus, estrogen plays a principal role in organ development, including a part in determining whether the fetus develops male or female sex organs. Thus, endocrine dismption can cause dismption of various reproductive and development processes and increase the possibiUty of certain kinds of carcinogenesis.  [c.229]

Vaccine candidates are based on the two viral surface proteins, gD and gB (80). Recombinant methods are used to express the proteins, either in Chinese hamster ovary (CHO) cells or in baculovims. The proteins are purified as subunits and formulated with different adjuvants. Clinical trials with these vaccine candidates have been performed, but the results to date have not been encouraging.  [c.359]

CHO = Chinese hamster ovary.  [c.229]

Aromatase inhibitors, which suppress estrogen production outside the ovaries, are useful for the treatment of tumors iu postmenopausal women. Tamoxifen (54) is very well tolerated and is considered the dmg of choice iu post menopausal patients. The progestational agents medroxyprogesterone (59) and megestrol acetate (60) ate used iu the treatment of endometrial tumors to block overstimulation of the ovaries by estrogen. Megestrol acetate has been reported to have utiUty iu reversing cachexia associated with cancer (31).  [c.443]

The increased use of chemotherapy as a modaUty in the treatment of cancer has caused a corresponding increase in the market for anticancer agents. Table 8 hsts the estimated 1990 worldwide sales for the most commonly utilized chemotherapeutic agents. Data for Japan are not included because of differences in medical and prescribing practices. Only a few anticancer dmgs have achieved sales in excess of 100 million per year and many of the dmgs discussed herein sell less than 10 million per year. Many of the approved dmgs were introduced early on in cancer chemotherapy for the treatment of lymphomas and leukemias. Because of lack of patent coverage and the relatively small market size, these dmgs are of relatively Htde commercial importance. Those agents which have achieved greater economic importance are newer, frequently used in combination chemotherapy, and of use in the treatment of soHd tumors which comprise the bulk of reported cancer incidence. A number of the agents in clinical trials, such as taxol (52) and camptothecin analogues, are expected to have considerable economic impact based on activity in the treatment of the more common human malignancies, eg, lung, breast, colon, and ovary.  [c.445]

Second and Third Generation Oral Contraceptives. Most oral contraceptives are combinations of an estrogenic agent and a progestational agent (progestogen). Estrogens are found in the ovary, and are important in preventing pregnancy they work in conjunction with the progestogen to suppress ovulation.  [c.112]

The estrogenic and progestational components provide thek primary contraceptive effect by blocking ovulation, ie, preventing the selection of a dominant foUicle in the ovary by a negative feedback action on the hypothalamus and pituitary. This inhibits pituitary secretion of follicle-stimulating hormone (ESH) [9002-18-0] and luteinizing hormone (LH) [9002-67-9], with the resultant inhibition of ovulation. The estrogen component also provides stabihty to the endometrium so that unwanted breakthrough bleeding can be avoided. This combination also provides several ancillary contraceptive mechanisms by interfering with fertilization and implantation processes should ovulation occur (7).  [c.112]

Tissue Plasminogen Activator from Mammalian Cell Culture. Tissue-type plasminogen activator or tissue plasminogen activator [105857-23-6] (t-PA) was originally identified in tissue extracts in the late 1940s (15). Other known plasminogen activators include streptokinase from bacteria, urokinase from urine, and prourokinase from plasma (16). In 1981 the Bowes melanoma cell line was found to secrete t-PA (known as mt-PA) at 100 X higher concentrations, making possible the isolation and purification of this enzyme in sufficient quantities that antibodies could be generated and assays developed to lead to cloning of the gene for this enzyme and subsequent expression of the enzyme in both E. coli and a Chinese hamster ovary (CHO) cell Je (15,17).  [c.44]

Embryo Cloning. A principal limitation to embryo splitting is that an embryo can be spHt only a few times before the pieces are too small to continue development. In contrast, embryo cloning can be used theoretically to make an unlimited number of copies of the same embryo (53). Cloned embryos are not limited by size because cells, housing a complete copy of the embryonic genome, are transplanted back into an oocyte that has had its nucleus removed. Therefore, the cell nucleus can become part of a new one-ceU embryo. This process is illustrated in Eigure 2b. A single cell from a 32-ceU embryo is removed using a widebore micropipette. Single-cell oocytes (unfertilized) are isolated from ovaries collected from slaughtered catde and are used as recipients for the cell from the 32-ceU embryo. Prior to the nuclear transfer, the oocyte nucleus is removed using a micropipette. The cell from the 32-ceU embryo is inserted next to the oocyte and the cytoplasmic membranes of the oocyte and cell are fused using a mild pulse of electricity. When the cell and the oocyte are joined, a single-cell embryo is formed that proceeds with normal development. If all the cells from the original 32-ceU embryo are transplanted, then 32 geneticaUy identical embryos can be produced. These embryos can be cultured in vitro and transferred to foster mothers or aUowed to develop and used to make more embryo clones. Therefore, numbers of identical cloned animals that can be produced from a single embryo are the o retie aUy limitle s s.  [c.243]

P and Pg, exist in foUicular fluid. Control of inhibin secretion involves a feedback relationship in which circulating FSH stimulates inhibin secretion, which in turn reduces the secretion of FSH (8). Both the homo- and the heterodimers of the P-subunits of inhibin promote the secretion of FSH and thus have been termed activins. Activin is secreted by the ovary and the testes into the circulation. In addition, both inhibin and activin have intragonadal autocrine and paracrine effects that influence gonadal steroidogenesis (9).  [c.172]

The primary sources of progesterone in women are the corpora lutea of the ovary and the placenta. Ovarian production of progesterone varies over the menstmal cycle. Baseline levels are 0.75-4 mg/d during the foUicular phase, ie, days 1—14 of a typical 28-d cycle. After ovulation and formation of the corpus luteum, production rises reaching peak levels of 15-50 mg/d midway through the luteal phase, ie, days 15—28 of the cycle (5—7). The plasma levels of progesterone reflect these differing rates of synthesis. FoUicular levels are <0.2-2.0 ng/mL and luteal levels range from 9.5-22 ng/mL (8,9). Peak levels of plasma progesterone persist for only 4—6 days, then rapidly decline to initial baseline levels. This drop in plasma progesterone triggers the onset of menses in 1—2 days. During pregnancy, placental production of progesterone exceeds that of the ovary by nearly 10-fold and the resulting plasma progesterone concentrations reach 120-200 ng/mL near term. In men and ovariectomized women, progesterone can be detected in the plasma at concentrations of 0.3-0.4 ng/mL (5—7).  [c.207]

The utems is exceptionally sensitive to the effects of estrogens and progestins. Estrogens stimulate the proliferation and vascularization of the uterine endometrium (see Hormones, estrogens and antiestrogens). Progestins serve to suppress the stimulatory effects of estrogen on uterine growth, an effect termed antiestrogenic. Progestins blunt the responsiveness of the utems to estrogen by reducing estrogen receptor levels in the utems (264,265). In addition, progestins affect estrogen metaboHsm within the utems by inducing 17P-hydroxysteroid dehydrogenase which converts estradiol to the inactive estrone (266). Morphologically, the uterine effects of progestins can be seen as a reduction in the number and size of endometrial glands and a decrease in the proliferation of both glandular and stromal cells (253,267,268). Progestins also act on the uterine myometrium reducing the frequency of contractions (269). In nonpregnant women, menstmal bleeding is the most noticeable effect of progestins on the lower reproductive tract. After being transformed from a proliferative to a secretory state by the action of progesterone or a synthetic progestin, the uterine endometrium requites constant steroidal stimulation or it regresses and is lost in menses. Intermenstmal bleeding, or breakthrough bleeding, is a common side effect with the use of synthetic progestins, as in oral contraceptives. Elsewhere within the lower reproductive tract, progestins have other effects. The quantity of cervical mucus is lessened and the mucus is more viscous under the influence of progestins (253). The motility of the oviduct is affected by progestins which can act to delay the transport of ova from the ovary to the utems (270).  [c.222]

Estrogen Receptor and Receptor-Mediated Molecular Events. Estrogen molecules are hpophihc and diffuse through the plasma membrane of all cells. The steroid ligands encounter their specific receptors only within target cells. In cells lacking estrogen receptors, estrogens are not readily retained and exit the cell. Estrogen receptors appear in target tissues before ovary maturation (53,54), and the concentration of estrogen receptor in the utems correlates with the level of estrogen in the blood (55). The number of estrogen-binding sites in the utems changes during the menstmal cycle from a minimum of 1000 sites per cell during estms (ovulation), increasing to 3500 sites per cell and reaching a maximum at proestms, which is immediately prior to the next cycle, of 5000 sites per cell. It has been reported that aging is associated with a decrease of estrogen receptor concentration (56). However, there is no decrease in binding affinity for estrogens. The affinity, specificity, and large concentration of estrogen receptors in cells allow a low concentration of estrogen to produce biological responses (57).  [c.241]

Biosynthesis. Natural estrogens are produced by steroidogenesis in various tissues. The ovary is the primary source of the hormone in nonpregnant women (69). Estradiol(3) is the most potent and primary product of the ovary, although the organ also produces estrone(2). The estrogens are ultimately formed from either androstenedione or testosterone as immediate precursors. The key reaction is the aromatization of the A-ring to yield a phenohc hydroxyl at C-3 (70). Pathological conditions, such as hirsutism and virilism, are thought to be caused by a defect of the aromatization reaction. During pregnancy the placenta produces large amounts of estrogens, especially estriol (4). Other tissues such as Hver, adipose tissue, skeleton muscle, and hypothalamus are also sources of estrogens where androgens are converted to estrone (71). In post-menopausal women, peripheral aromatization of adrenal androgens to estrone is the principal source of estrogen (72). Because significant extraglandular estrogen production occurs in adipose tissue, estrogen production is greater in obese than in thin post-menopausal women, and total estrogen production in the massively obese may be as great as, or greater than, in premenopausal women (73).  [c.242]

Pharmacological Effects. Three principal natural estrogens (E, E2, and E ) are produced by the ovary and play important roles in the development and support of female reproduction (65). The normal menstmal cycle is modulated by a variety of ovarian steroids and peptides, among which estrogen is a primary regulator. CeUs in the anterior hypothalamus secrete gonadotropin-releasing hormone (GnRH, also known as luteinizing hormone releasing hormone, LHRH) in a pulsating manner. LHRH stimulates the gonadotrope ceUs of the anterior pituitary to release both luteinizing hormone (LH) and follicle-stimulating hormone (ESH). These pituitary gonadotropic hormones induce maturation of the oocyte (an ovarian ceU which produces an ovum) and stimulate the ovarian folHcles to synthesize estrogen and progestins as well as the peptide hormone inhibin. Estrogen and progestins directiy inhibit LHRH and pituitary gonadotropin secretion and inhibit further stimulation of the ovary (83). The effect of estrogen on pituitary gonadotropin is biphasic. Early in the cycle when the concentration of estrogen is relatively low (20 60 pg/mL), estrogen inhibits LH secretion. The increasing concentration of estrogen in midcycle (200 pg/mL) leads to an increase of the frequency and ampHtude of the LH pulse. The LH surge leads to ovulation of the dominant folHcle and coincides with a transient decrease in estrogen levels. Ovulation typically occurs on day 14 of the typical 28-d cycle. The period after ovulation is the luteal phase, which is characterized by a decreasing LH pulse and a rise in progesterone concentration (83,84).  [c.242]

Safety. X-rays are classified as ionizing radiation. These photons possess sufficient energy to ionize molecules leading to bond breakage and the formation of free radicals. There has been increasing concern about the safety of x-ray medical imaging since the 1970s. The most significant concern centers on radiation dose obtained in x-ray imaging session. In addition to the short-term effects of the radiation, there also is concern about the long-term effects. For example, the abdomen of a premenopausal woman is rarely imaged because of potential damage to the ovaries. Significant advances have been made in decreasing the exposure from x-rays during a plane film imaging session. Radiation exposure during plane film imaging decreased approximately 20-fold from 1960 to 1994. Radiation exposure from CT imaging has, however, increased by a factor of two to three since the first generation CT scanners (28). Table 1 fists the approximate dose obtained from various x-ray imaging procedures to specific body tissues.  [c.51]

Because it is the nitro alcohol with greatest potential for human exposure, additional testing of 2-hydroxymethyl-2-nitro-l,3-propanediol has been conducted. In a 90-day dermal study in rats, no effects were observed with animals exposed to 1000 mg/kg/d except for a slight yeUow staining at the site of appHcation. No teratogenic effects were noted in either rats or rabbits when tested by gavage. Additionally, 2-hydroxymethyl-2-nitro-l,3-propanediol was not found to be mutagenic in in vitro tests, ie, the salmonella reverse-mutation test, a chromosome aberration study with Chinese hamster ovary ceUs, and in an unscheduled DNA synthesis study with primary rat hepatacytes.  [c.61]

Nuts, as generally defined, are hard-sheUed seeds enclosing a single edible oily kernel. Most of the common nuts fall within this classification. Many species, however, differ gready in size, structure, shape, composition, and davor. A more technical definition of a nut is a hard, one-seeded fmit developed from many carpels united to form a compound ovary, the woody pericarp of the shell remaining closed at maturity. Examples are the beechnut, butternut, chestnut, hickory nut, pecan, and walnut, which are all tme nuts. The word nut, moreover, is appHed indiscriminately to many seeds, fmits, and tubers having hard coverings, as well as to single oily or starchy kernels such as those of the almond, Brazil nut, cashew, chufa, coconut, Hchee, peanut, picon, and pistachio, which do not fit the more technical definition. Although in common padance, the term nut implies edibiUty (1), nuts of many kinds are grown not only for food but also as sources of oil and for medicinal, ornamental, and other uses. Table 1 Hsts many nuts from various parts of the wodd.  [c.268]

Different types of cells can be protected by thiols to different degrees. WR-1065 protects normal human fibroblasts, but not fibrosarcoma tumor cells, against the DNA-damaging and lethal effects of x-irradiation in vitro (18). CeU-type differences in chromatin organisation and DNA-dmg associations may be responsible. WR-1065 also protects the DSB-repair-deficient xrs5 Chinese hamster ovary (CHO) mutant much less efficientiy than the parent line against killing by x-rays and neutrons (19). In contrast, WR-1065 has an equally protective effect on two human ghoblastoma lines (20), one of which is DSB-repair-deficient because of a defective DNA-dependent protein kinase activity. Two human squamous cell carcinoma lines, which have different DSB-repair capabiUty, are also protected equally by MEA (8).  [c.488]

Estrogens. Estrogens were originally isolated between 1929 and 1935 and are characterized by having an aromatic A-ring and thus having a phenohc character. Estrogens stimulate the growth and development of the female reproductive organs and the secondary sex characteristics. Another primary function of estrogens along with progesterone, is to regulate the ovulatory cycle. Estrogens, as with all the steroid hormones, are important for healthy growth and development in women and men. The main production site of estradiol [50-28-2] (25) is the female ovary however, small amounts of estrogens are produced in testes and the adrenal cortex, and significant amounts of estrogens are produced by peripheral aromatization of local and circulating androgens in skin and fat. Estrone [53-16-7] (26) and estriol [50-27-1] (27) are estrogenicaHy active metaboUtes of estradiol. Synthetic and natural estrogens play an important role in the treatment of osteoporosis in post-menopausal women. Antiestrogens are important for the treatment of breast  [c.417]

Progestins. Progesterone [57-83-0] (28), the principal progestin ia mammals, is secreted primarily by the corpus luteum of the ovary. A main responsibihty of progesterone, together with estrogen, is to prepare the endometrium for pregnancy. Synthetic progestias have wide appHcations ia gynecology and contraception (52—57).  [c.418]

Composition and Methods of Manufacture. Hepatitis B vacciaes consist predomiaandy of 22-nm particles of the S antigen of the Hepatitis B surface antigen. Some vacciaes also iaclude varyiag amounts of pre-Sl and/or pre-S2 antigens that are precursors to the tiiUy matured surface antigen of this vims. The antigen can be detived from the plasma of chronic carriers usiag plasma fractionation techniques that ensure purity and iaactivation of any unwanted Hve agents, or more commonly from recombinant organisms. There are systems usiag recomhinants of yeasts or Chinese hamster ovary (CHO) cells that can be used to produce the surface antigen on a large scale (24—26).  [c.358]

Kinetics of Cell Growth and Product Formation. Mammalian cells grow at a much slower rate than bacterial and yeast cells (see Yeasts). The maximum specific growth rates for mammalian cells range from 0.01 to 0.05 h , corresponding to cell doubling times of 14 to 70 hours depending on the cell line and environmental conditions. Most primary cell lines are anchorage dependent and need a surface to grow on. They are also contact inhibited, ie, they stop growing once the surface is confluent. Alternatively, most of the cell lines used industrially for recombinant products and monoclonal antibodies are not attachment dependent. Eor example Chinese hamster ovary (CHO) cells are commonly used as host cells for recombinant products. These cells are transformed by tumor vimses and do not require a surface to grow on. They do, however, prefer to grow on surfaces and requirement for semm factors diminishes significantly when they are attached to surfaces. Thus CHO cells can be cultured for several weeks in protein-free media if grown on microcarriers, whereas they require semm proteins such as fetuin to grow in suspension. Most hybridomas used for making monoclonal antibodies are attachment independent, grow in suspension, and have minimal requirement for semm proteins. It is necessary to adapt these cells to semm-free media for several days before they start growing well in these media.  [c.229]

Hormones. Although not stricdy cytotoxic, hormones (qv) have been used to control the environment of hormone dependent tumors such as those of the prostate, breast, and endometrium (29), ie, androgens are used to control the growth of estrogen dependent breast tumors, whereas estrogens control androgen dependent tumors of the prostate. Hormones that have anticancer activities are Hsted ia Table 6. Stmctures are shown ia Figure 7. In addition to the steroidal hormones (57, 59—62) several nonsteroidal hormones have been iatroduced (54—56) as have leuteniziag hormone-releasing hormone (LHRH) agonists. These are often used ia combiaations. For example, LHRH analogues (63,64), antiestrogens (54), aromatase inhibitors (62), and progestins all are used in the control of breast cancer (30). LHRH analogues suppress estrogen production in the ovaries and are used in premenopausal breast cancer patients.  [c.442]

See pages that mention the term Ovaries : [c.161]    [c.206]    [c.286]    [c.44]    [c.169]    [c.169]    [c.170]    [c.224]    [c.200]    [c.229]    [c.435]    [c.437]    [c.437]    [c.437]    [c.437]   
12 Endocrine Disrupting Chemicals (1999) -- [ c.8 , c.38 ]