Search PubMed⌕ Search

Biomedical subjects

V C Stevens

Publications and source records attributed to V C Stevens.

At least 55 records · Page 3Linked to original sources

Effect of synthetic thyrotropin-releasing hormone on ovulation in baboons.

Twice daily oral thyrotropin-releasing hormone administered to female baboons throughout the menstrual cycle had no significant influence on cycle length or upon estrogen levels but produced blunted midcycle LH peaks and luteal phase progesterone levels in three fourths of the treatment cycles. Mean plasma prolactin levels were increased approximately 2.5-fold relative to untreated, ovulatory control cycles. CB-154 alone did not alter cycle length or endocrine parameters examined (mean prolactin levels were decreased but not significantly). Cycles during which CB-154 was administered concomitantly with TRH were characterized by normal ovulation as evidenced by luteal phase progesterone levels. Since the effect on LH secretion was reversed by concomitant CB-154 administration, TRH-induced anovulation in animals given long-term treatment appeared to be mediated through physiologic mechanisms sensitive to elevated circulating prolactin levels. However, this conclusion must be considered equivocal since prolactin levels were also elevated during ovulatory cycles following long-term TRH therapy. Finally, these data do no exclude the alternative possibility that anovulation in baboons given long-term TRH treatment was a reflection of thyroid disturbance and not directly attributable to elevated prolactin.

Animals↗

Disordered nocturnal prolactin regulation in women with breast cancer.

Mean 24-hr prolactin concentrations were determined in 25 female control subjects, 16 women with benign breast masses, and 23 subjects with breast cancer. This evaluation performed before breast surgery revealed significantly decreased (p less than 0.02) nocturnal (12 a.m. to 7 a.m.) prolactin concentrations in 12 postmenopausal breast cancer subjects that contrasted with significantly increased (p less than 0.05) nocturnal prolactin levels in five luteal-phase premenopausal women with breast cancers. Prolactin concentrations in patients with benign breast disease were not significantly different from control subjects. Two of the premenopausal breast cancer patients had marked preoperative elevations in their mean 24-hr prolactin levels, and they were two of the three subjects who have since expired. Nocturnal prolactin secretion was significantly decreased (p less than 0.03) in four premenopausal breast cancer patients when they were studied 1 year after surgery; however, it remained the same in the eight postmenopausal breast cancer patients similarly evaluated. Although disordered prolactin regulation has been found in these women with breast cancer, its role in the etiology and progression of human cancer is still uncertain.

Adult↗

Twenty-four-hour preoperative endocrine profiles in women with benign and malignant breast disease.

Mean 24-hr growth hormone, luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone concentrations determined preoperatively in 16 women with benign breast masses and 17 patients with breast cancer were similar to those levels found in 25 age- and weight-matched control subjects. Mean 24-hr testosterone levels, however, were significantly elevated in women with breast cancer evaluated in the luteal phase of their cycles and were normal in postmenopausal breast cancer women. In addition, serum thyroid-stimulating hormone, thyroxine, cholesterol, and triglyceride levels were normal in these subjects. Plasma cortisols and urinary 17-hydroxysteroid excretion tended to be higher in both the benign and malignant breast disease group and probably reflected preoperative anxiety. Hence, we have found normal concentrations of a variety of endocrine and other biochemical agents that can stimulate breast tissue growth and/or have been previously reported to be disordered in women with breast cancer.

Adult↗

Serum levels of a placental protein during gestation in the baboon.

A placental specific protein (Sp-1) isolated from human placentas was used to establish a radioimmunoassay for measurement of a baboon protein in the sera of pregnant baboons. No reaction was observed with any known pituitary or placental hormone in this assay system. Levels of Sp-1 were detected at 17 to 18 days of gestation and reached high levels by the end of the first trimester of pregnancy. A slow increase in serum levels continued thereafter until parturition. Disappearance of Sp-1 post partum was very slow and required 26 to 34 days to become undetectable in the serum. No function or role of Sp-1 in pregnancy has been suggested, but possible use of its measurement for detecting abnormal placental function deserves investigation.

Animals↗

Purification and properties of the subunits of human pituitary follicle-stimulating hormone.

Highly purified human pituitary FSH was partially dissociated by treatment with 8M-urea, and alpha- and beta-subunits were isolated by ion-exchange chromatography and gel filtration. Tests of biological activity by in-vivo assays and in-vitro radioreceptor assays were in good agreement and showed that preparations of isolated alpha-subunit had less than 1%, and beta-subunit from 2 to 10% of the FSH activity of the intact hormone. In contrast to results reported elsewhere, most of the subunit preparations reassociated with counterpart subunit to regain biological activity equal to that of intact FSH (around 160 mg NIH-FSH-S1/mg). The intact FSH recovered as a by-product after isolation of subunits was of high biological activity, and its LH contamination was reduced by more than 90% when compared with thepurified FSH starting material. The subunits are relatively inactive in a radioimmunoassay specific for intact FSH. Sialic acid and tryptophan determinations indicated that both subunits contain sialic acid and that tryptophan is present only in the beta-subunit.

Chromatography, DEAE-Cellulose↗

The effect of indomethacin of HMG-HCG induced ovulation in the phesus monkey.

The investigation was designed to study the influence of indomethacin on gonadotropin induced ovulation in the rhesus monkey. Six mature female monkeys were treated with HMG-HCG for at least 2 control ovulatory cycles at dosage levels adjusted to induced ovulation while avoiding superovulation. Ovulation was confirmed by observation of the ovaries for fresh ovulation points at laparotomy. Following establishment of an appropriate dosage schedule, treatment was begun with indomethacin (5 mg/kg/day) starting 5 days prior to HCG and continuing to the time of laparotomy. In a second treatment cycle, indomethacin was administered at a dose of 5 mg/kg b.i.d. together with the established dose of HMG-HCG. Ovarian inspection was carried out as in the control cycles. Venous blood was obtained on treatment days 4, 7, 10 and 11 for determination of serum estrone, estradiol and progesterone. Indomethacin administration resulted in ovulation inhibition at a dose of 10 mg/kg/day when ovulation inducing doses of gonadotropins were administered. Peripheral blood steroid levels suggest that follicle maturation and estrogen production was unimparied by indomethacin. These findings indicate that the ovarian synthesis of prostaglandin may be essential in the process of ovulation.

Animals↗

Effectiveness of prostaglandin f 2 alpha in restoration of HMG-HCG induced ovulation in indomethacin-treated rhesus monkeys.

Six mature female rhesus monkeys were treated with HMG-HCG in control cycles at doses adjusted to induce ovulation while avoiding superovulation. Occurrence of ovulation was determined by observation of fresh ovulation points at laparotomy 48 to 120 hours following HCG. In subsequent cycles animals were treated with indomethacin (treatment days 4 through 10) together with the established dose of HMG-HCG. In 8 cycles indomethacin 5 mg/kg was given i.m. once daily; in 9 cycles 10 mg/kg i.m. was administered in 2 divided doses. Following this, PGF2alpha (3 mg t.i.d. s.c.) was administered for 3 days together with indomethacin 10 mg/kg and HMG-HCG, beginning on the day prior to HCG. Determinations of progesterone were performed by RIA on treatment days 4, 7, 10, and 11. Eleven of the 13 control cycles were ovulatory. With indomethacin 5 mg/kg/day, 5 of 8 cycles were ovulatory but ovulation was delayed in 2 instances. Of 9 cycles using indomethacin 10 mg/kg/day only 1 was ovulatory. When PGF2alpha was administered in susequent cycles along with indomethacin (10 mg/kg) and HMG-HCG, ovulation occurred in 13 of 19 cycles. These data suggest that local ovarian PGF2alpha may be essential in the mechanics of follicle rupture in gonadotropin-treated rhesus monkeys.

Animals↗

The effect of immunizing female rats with modified rat pituitary extract.

Immune reactions to a number of hormones have been induced, but information is lacking on the feasibility of inducing immune reactions to homologous gonadotropins. Female rats immunized with diazotized and tyrosylated rat pituitary extract containing gonadotropic activity and emulsified in complete Freund's adjuvant expressed various reproductive disturbances such as increased cycle length (7.0 days), increased number of sterile matings, reduced implantation in animals becoming pregnant, and reduced ability to carry fetuses to term. These effects were not exhibited by rats immunized similarly with diazotized or tyrosylated rat pituitary extract containing no detectable gonadotropic activity. Rats not becoming pregnant had a significantly higher antibody level to rat luteinizing hormone than did rats becoming pregnant. No significant elevation of rat follicle-stimulating hormone antibodies was noted. It is concluded that auto-immune reactions to gonadotropins can be induced and that very low levels of antibodies have a significant effect on reproduction.

Animals↗

Fertility control through active immunization using placenta proteins.

Numerous studies have demonstrated that antibodies to placental proteins in a variety of species are capable of preventing or disrupting gestation. Early work in this area was primarily directed towards the passive immunization of rodents with heterologous antisera to whole placental extracts. Toxicity and renal damage often accompanied fertility inhibition. More recent studies reported less toxicity and a higher specificity of antibodies to reproductive function when anti-placental antibodies were absorbed with serum and extracts of non-reproductive organs. Few studies have been reported in which active immunization with placental proteins was employed. The most detailed studies of active immunization have employed highly purified placental hormones. Immunizations of rats and rabbits with human placental lactogen have resulted in marked reduction in reproductive function. Immunization of human females with chemically altered (hapten-coupled/ HCG resulted in the production of antibodies reacting with unaltered HCG and pituitary LH. These antibodies were capable of reducing the level of endogenous serum LH in pre- and post-menopausal women. The also altered the events of the menstrual cycle in premenopausal women. More specific inhibition of chorionic gonadotrophin has been obtained by immunization of baboons with the beta subunit of HCG. Antifertility effects without alterations in the menstrual cycle of female baboons immunized with the beta subunit of HCG have been reported. The antibodies produced in these animals reacted significantly with human LH in vitro. The possibility of using hormonal and non-hormonal placental proteins as antigens for the specific immunological inhibition of fertility remains.

Abortion, Spontaneous↗