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Biomedical subjects

R W Rebar

Publications and source records attributed to R W Rebar.

At least 73 records · Page 4Linked to original sources

Triple-X syndrome and premature ovarian failure.

Two patients with 47,XXX karyotypes and premature ovarian failure are described. Both presented with episodes of amenorrhea, elevated levels of circulating follicle-stimulating hormone and luteinizing hormone, and decreased estrogen concentrations. However, evidence of follicular activity existed in both cases. Why some women with 47,XXX karyotypes suffer from premature ovarian failure and why others have normal fertility and normal lengths of reproductive function is not known. Reports of immunologic disorders in patients with the triple-X syndrome and data showing that control of the lymphocyte may be related to the X chromosome point to a possible link between premature ovarian failure in 47,XXX women and immunologic abnormalities.

Adult↗

Neuroendocrine control of the postpartum period.

This postpartum period is characterized by stimulation of lactation and suppression of ovulation. During pregnancy a number of hormonal changes prepare the breasts for lactation following delivery. The process of lactation is functionally related to the suppression of ovulation. These two physiologic changes observed in the puerperium are considered in detail in this review.

Amenorrhea↗

Treatment of hirsutism with spironolactone.

Clinical and endocrine evaluations of 39 patients with hirsutism were performed to determine the effectiveness and site(s) of action of an antiandrogenic compound, spironolactone. Treatment with spironolactone at a dose of 200 mg/day resulted in a clear beneficial effect on the quantity and quality of facial hair growth in 19 of 20 patients with moderate to severe hirsutism. Regression of hirsutism in terms of diameter, density, and the rate of facial hair growth was noticeable within two months. The maximal effect was observed at six months and was maintained at 12 months of treatment. Spironolactone was equally effective in reducing hirsutism in women with polycystic ovary syndrome and idiopathic hirsutism. These clinical observations were associated with a prompt and sustained reduction in levels of androgen of ovarian origin without affecting levels of adrenal androgen and cortisol. Apart from diuresis, which was limited to the first few days of treatment, there were no discernible side effects the one year of this study. Our results indicate that spironolactone is a highly effective and safe agent for the treatment of hirsutism through its inhibitory action on both ovarian androgen secretion and peripheral androgen action.

Amenorrhea↗

The effect of luteinizing hormone-releasing factor and its agonist on cultured human granulosa cells.

The possible direct effect of luteinizing hormone-releasing factor (LRF) and a potent LRF agonist, [D-Trp6,Pro9NEt]-LRF (LRF-Ag), on basal and follicle-stimulating hormone (FSH)-stimulated estrogen and progesterone production by cultured human granulosa cells was examined. Granulosa cells, collected from healthy follicles (4 to 12 mm in diameter) in the early to midfollicular phase were grown for 2 days in serum-free medium with aromatase substrate (androstenedione; 10(-7) M) and human FSH (100 ng/ml), LRF (10(-10) to 10(-7) M) or in LRF-Ag (10(-7) M). Granulosa cells from each follicle responded to FSH stimulation by showing marked increases (2- to 20-fold) in estrogen and progesterone production. Concomitant treatment with high doses of LRF or LRF-Ag did not alter the steroidogenic effect of FSH. These results suggest that in contrast to the rat, LRF and its agonistic analog do not act directly on human granulosa cells to inhibit acute steroidogenic function.

Adult↗

Hormonal basis of reproductive defects in athymic mice: reduced gonadotropins and testosterone in males.

We wished to determine if congenitally athymic nude male mice have the same reduction in circulating concentrations of gonadotropins and gonadal steroids observed in their female counterparts when compared to their normal heterozygous littermates. We therefore quantitated pituitary and circulating concentrations of gonadotropins and circulating levels of testosterone in 102 congenitally athymic mice and 101 of their heterozygous littermates ranging in age from 1 to 120 days. Although the developmental patterns observed for both circulating luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were similar to those previously observed in rats and mice, the athymic mice had significantly reduced concentrations of both pituitary and serum LH and FSH in comparison to the heterozygotes. In general, the reduced secretion of gonadotropins was most marked prior to sexual maturation but persisted in adult athymic males. Circulating concentrations of testosterone were also markedly reduced in the adult athymic males. Histologically, the number of Leydig cells appeared reduced in testes from 20-day-old athymic mice. However, no differences could be detected in testes from 40-day-old animals, and spermatogenesis appeared normal. Thus, unlike athymic females, athymic male mice appear to have normal reproductive capacity despite these hormonal abnormalities.

Animals↗

Sleep-associated gonadotrophin and oestradiol patterns in girls with precocious sexual development.

Circulating concentrations of gonadotrophins and oestradiol (E2) during sleep were examined in six girls aged 5-10 years with precocious sexual development. All subjects exhibited nocturnal increments of LH and/or FSH. Gonadotrophin secretion appeared to vary from pulsatile release to random oscillations. Three subjects with LH pulses of greater than 5 miu/ml and a concomitant FSH rise had a temporal elevation of E2 during sleep. The other three subjects with pulses of either LH or FSH of less than 5 miu/ml had no nocturnal rise in E2. These data suggest that the nocturnal elevation of E2 results from pituitary release of both LH and FSH, leads to premature sexual development, and may be occasioned by inappropriate timing of hypothalamic gonadotrophin-releasing hormone (LHRH) secretion.

Child↗

The thymus gland and reproduction: do thymic peptides influence the reproductive lifespan in females?

Thymic hormones may play an important role in determining the reproductive lifespan in females. Thymic peptides can release gonadotropin-releasing hormone (GnRH) from the hypothalamus and thus luteinizing hormone (LH) from the pituitary gland in vitro. Independent data are also accumulating to show that gonadotropins may be necessary to prevent atresia of primordial follicles in utero. It is possible that thymic peptides regulate the release of GnRH-LH in utero in women and are important in determining the rate at which primordial follicles and oogonia are lost. Thus, thymic peptides may play a role in fixing the number of oocytes available for ovulation during the reproductive lifespan.

Adolescent↗

Evidence for an influence of the ovary on circulating dehydroepiandrosterone sulfate levels.

Circulating dehydroepiandrosterone sulfate (DS) declines in old age, falling to almost undetectable levels after the seventh decade. Since an accelerated decrease occurs after the menopause, we sought to determine whether ovarian factors may influence adrenal DS secretion independent of chronological age. DS, cortisol, and estradiol levels were compared in subjects grouped according to age, ovarian function, and estrogen replacement. Our data show that premature ovarian failure and ovariectomy in young as well as in postmenopausal subjects precipitate an earlier decline in DS levels. There were no accompanying changes in cortisol levels and no correlations among levels of DS, cortisol, and estradiol. Long term estrogen replacement (over 10 yr) in postmenopausal women over age 65 had no beneficial effect on the age-related DS decline. We suggest that ovarian factors separate from estrogen-mediated effects significantly influence the reduction of DS levels independent of age.

Adult↗

Idiopathic premature ovarian failure: clinical and endocrine characteristics.

The characteristics of 26 patients with presumptive premature ovarian failure have been examined. The initial diagnosis was based on any single serum follicle-stimulating hormone (FSH) concentration of greater than 40 mIU/ml in karyotypically normal women under 35 years of age with irregular menses or amenorrhea. Clinical manifestations were heterogeneous: some failed to undergo pubertal maturation, and other developed hypergonadotropic amenorrhea following several years of regular menses. Almost 70% experienced hot flashes. Three had thyroiditis. Nine of 18 patients had hormonal evidence of functioning ovarian follicles, and 4 of 9 women had viable oocytes on biopsy. Evidence of ovulation was noted in five patients, and spontaneous pregnancy occurred in one. These data emphasize the fallacy of using elevated FSH levels to diagnose irreversible ovarian failure and indicate the possibility of ovulation and pregnancy in some affected individuals.

Adult↗

Hypergonadotropic amenorrhea and premature ovarian failure: a review.

Amenorrhea with hypergonadotropinism consists of several distinct disorders. Affected individuals should be investigated thoroughly and not merely told they have ovarian failure. Accumulating evidence suggests that some women with "premature ovarian failure" do indeed ovulate again and even conceive. Thus, elevated levels of circulating gonadotropins can no longer be regarded as establishing that the ovaries are devoid of all oocytes. Delineation of all of the causes of hypergonadotropic amenorrhea and the establishment of rational means of inducing ovulation in women with follicles remaining are clearly tasks for present and future investigations.

Adrenal Hyperplasia, Congenital↗

Thymosin stimulates secretion of luteinizing hormone-releasing factor.

Partially purified thymosin fraction 5 and one of its synthetic peptide components, thymosin beta 4, but not thymosin alpha 1, stimulated secretion of luteinizing hormone--releasing factor from superfused medial basal hypothalami from random cycling female rats. In addition, luteinizing hormone was released from pituitary glands superfused in sequence with hypothalami. No release of luteinizing hormone in response to thymosin was observed from pituitaries superfused alone. These data provide the first evidence of a direct effect of the endocrine thymus on the hypothalamus and suggest a potentially important role for thymic peptides in reproductive function.

Animals↗

The hormonal basis of reproductive defects in athymic mice: diminished gonadotropin concentrations in prepubertal females.

Congenitally nude athymic female mice are known to have severe deficiencies in reproductive function, including reduced ovarian weight, increased follicular atresia, decreased fertility, and premature ovarian failure, in comparison to their phenotypically normal heterozygous littermates. To determine the hormonal basis for these reproductive defects, pituitary and circulating concentrations of gonadotropins and circulating levels of gonadal steroids were quantitated in 132 congenitally athymic mice and 126 of their normal heterozygous littermates, ranging in age from 1-120 days. Although prepubertal increases in both circulating LH and FSH, which were maximal at 10 days of age, were observed in both athymic and heterozygous females, the concentrations were reduced significantly in the athymic animals (P less than 0.01). Dramatic increases in the pituitary concentrations of both LH and FSH followed at 20 days, with the concentrations in heterozygotes being 3-fold greater than those in the athymic mice (P less than 0.01 for LH; P less than 0.001 for FSH). These abnormalities in pituitary gonadotropin concentrations in the athymic mice were followed by a 2- to 3-fold reduction in the secretion of estrone but not estradiol in athymic females 30 days and older. Serum androgen levels were also reduced. From these data we infer that the reduced gonadotropin concentrations observed in the athymic animals are responsible for their increased follicular atresia and premature ovarian failure and that the thymus gland appears to be essential for normal development of the hypothalamic-pituitary-ovarian axis.

Animals↗

Impact of acute surgical stress on anterior pituitary function in female subjects.

The effects of acute surgical stress and the accompanying anesthesia on anterior pituitary function in female subjects was studied by means of frequent perioperative determinations of the circulating concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), growth hormone (GH), and thyroid-stimulating hormone (TSH). No appreciable alteration in the circulating concentrations of either LH or FSH could be detected. In contrast, the levels of PRL and GH were found to be markedly increased during the perioperative period, with the increase in pRL invariably preceding any noticeable alteration in GH levels. In addition, perioperative PRL but not GH levels were significantly higher (p < 0.01) in patients undergoing a major surgical procedure, in contrast to a minor one. Finally, this study furnishes detailed evidence of a small but significant (p < 0.05) increase in TSH levels in patients undergoing a major surgical procedure. These data indicate that augmentation of pituitary secretion of three stress-related hormones, but not gonadotropins, occurs during surgical procedures.

Adult↗

Protein A as an immunoadsorbent in radioimmunoassay: usefulness in a rapid assay for urinary luteinizing hormone.

A staphylococcal cell wall protein, designated protein A, is known specifically and rapidly to bind to immunoglobulin G. We have utilized this protein as an immunoadsorbent to separate antigen-antibody complexes from free antigen in a rapid 6-hour radioimmunoassay for urinary human luteinizing hormone (hLH). We have further documented the efficacy of this system and the optimal conditions for this assay. The ability of this assay to provide rapid and reliable measurements of hLH in timed urinary specimens provides a useful tool for determination of the preovulatory LH surge and prediction of the time of ovulation in women.

Antigen-Antibody Complex↗

Reduced gonadotropins in athymic mice: prevention by thymic transplantation.

The reduction in pituitary concentrations of gonadotropins observed in 20-day old congenitally athymic nude mice in comparison to their normal heterozygous littermates was completely prevented in females and partially prevented in males by thymic transplantation on the first day of life. Those athymic mice receiving transplants but in which no thymic tissue could be found at sacrifice had reduced pituitary gonadotropin concentrations equivalent to sham-operated athymic animals. From these data we infer that the reduced concentrations of gonadotropins seen in the athymic animals are causally related to the absence of the thymus and suggest that the thymus, directly or indirectly, is necessary for development of normal function of the hypothalamic-pituitary-gonadal axis in mice.

Animals↗