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Negative feedback regulation of gonadotropin secretion by androgens in fetal rhesus macaques.

Previously we described sex differences in circulating gonadotropin concentrations (greater in females) in fetal rhesus macaques, and demonstrated that these sex differences relate, at least in part, to the negative feedback actions of testicular secretions. A fully functional gonadal-hypothalamic-pituitary feedback relationship is present as early as Day 100 of gestation in fetal males because castration at this time results in a dramatic increase (greater than 10-fold) in fetal luteinizing hormone (LH) concentrations. Although short-term (6-h) treatment of fetuses with testosterone (T) 3 wk after gonadectomy (GX) does not lower LH levels in males, it is completely effective in females. These data suggest that either T is not the primary testicular factor responsible for feedback suppression of LH in fetal males, or the hypothalamic-pituitary axis becomes insensitive to T after GX. To determine if immediate treatment with T after GX is effective in maintaining LH levels, we gonadectomized five fetal rhesus males on Days 98-104 of gestation and immediately implanted crystalline-T-containing intraabdominal Silastic capsules. An additional five fetuses were treated with the nonaromatizable androgen dihydrotestosterone (DHT). Umbilical arterial samples for hormone analysis were obtained prior to GX and again approximately 3 wk later. Serum from control males (n = 11) castrated in utero on Day 100 of gestation contained significantly greater concentrations of LH and follicle-stimulating hormone (FSH) 3 wk after the operation than before GX. Five sham-operated male fetuses did not have elevated levels of either LH or FSH in their serum on Day 120 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ovarian follicular dynamics in the llama.

Ovarian follicular dynamics were determined in adult llamas by ultrasonography and palpation per rectum and hormone analysis (estradiol-17 beta and estrogen conjugates) of plasma and urine. The relationship of gonadotropin secretion to follicular development was determined by the analysis of plasma FSH and LH concentrations. Progesterone analysis of plasma was used to verify or deny the presence of CL. Final follicular development (from 3 mm) averaged 4.8 days, while the duration of the mature follicle (8-12 mm) averaged 5.0 days; regression of the follicle occurred over about 4 days. The development of a subsequent dominant follicle usually began within 2-3 days after onset of regression of the dominant follicle. While several follicles were present at the time of the demise of the dominant follicle, only one follicle continued to develop. The interval between ovarian follicle waves averaged 11.1 days. Dominant follicle activity alternated between ovaries in 81% of the cycles. The occurrence of dominant follicles was evenly distributed between ovaries. While plasma estradiol and estrogen conjugate concentrations were positively associated (p less than 0.05) with follicular activity, urinary estrogen conjugate concentrations best reflected ovarian follicular dynamics (p less than 0.001). Daily FSH concentrations in plasma were not correlated with follicular activity. LH concentrations in plasma were low in all animals throughout the study, indicating estrogen from developing ovarian follicles does not induce the release of LH. Progesterone values were low during the study, indicating that the llama does not spontaneously ovulate, at least under the conditions of this study. In summary, llamas have overlapping ovarian follicle waves that occur at about 11-day intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Testicular volume, semen profile and serum hormone levels in fertile Thai males.

The fertility profile of 307 Thai male volunteers whose wives were currently in early pregnancy was established by genital examination, semen analysis and serum hormone analysis. Ninety percent of the subjects had testicular volumes of 12-25 ml (mean 17.2 ml) which was found to relate to body weight, height and the ponderal index as well as to the sperm count. However, values for semen analysis were significantly below the recognised standard for Caucasian males. There was an inverse relationship between testicular volume and the serum concentration of FSH, LH and prolactin. It is suggested that a common protocol for male fertility assessment should be used to establish standard parameters for racially different male populations.

Adolescent↗

Hormonal response to electrocautery of the ovary in patients with polycystic ovarian disease.

Fifty-eight women with polycystic ovarian syndrome (PCO) were treated with electrocautery of the ovarian capsule and then studied by hormone analysis for 12 months. In 72% ovulation appeared to occur within 4 weeks and in this group mean serum LH and FSH levels showed a statistically significant increase the day after electrocautery, followed by a gradual decline in LH to a level significantly below the pretreatment value. No changes in LH and FSH were seen in those who did not ovulate. The mean levels of testosterone, androstenedione and dihydrotestosterone which were in the upper normal range or slightly above before treatment were significantly reduced after electrocautery. Serum oestradiol levels showed a significant increase after 1 week, when progesterone levels were still unchanged, suggesting that follicular development was already in progress. The mean serum level of sex hormone binding globulin was slightly below the normal range before treatment and then increased gradually. Endocrine responses to electrocautery were similar to those described previously after wedge resection. The simplicity of this treatment and the good response make it an attractive alternative for treating infertility associated with PCO.

Androstenedione↗

Hormone studies in females with androgenic hairloss.

Reports on hormone analysis in androgenic hairloss in the female show partly contradicting results. Elevated as well as normal-range androgen levels have been found. The present study aimed at the investigation of a possibly more differentiated hormonal constellation by hormone analysis and additional determination of the hypophyseal level by the thyrotropin-releasing hormone (TRH) test. In 46 female patients with androgenic hairloss blood sampling for hormone analysis was performed. Determination of the androgens testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), 17-hydroxy-progesterone acetate (17-OHP) and free testosterone (FT), of sex-hormone-binding globulin (SHBG), estradiol (E2), cortisol (F) and the hypophyseal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was performed by standard radioimmunoassay methods. The TRH-test is based on feedback mechanisms between the hypothalamic TRH which stimulates hypophyseal TSH and PRL release. Thus, even mild forms of hypothyroidism or hyperprolactinaemia can be detected. The control group for the TRH test consisted of 45 volunteer females without hairloss or any other hormonal or menstrual disturbances. Statistical analysis was performed according to the Wilcoxon two-sample test. The results of the study show no significant elevation of androgens in females with androgenic hairloss, but a more complex condition with involvement of the glandula suprarenalis and the hypophyseal level. Significantly elevated TSH levels prior to and after TRH stimulation in the hairloss group indicate that hypothyroidism may be an important hormonal disturbance in androgenic hairloss. Interactions between hypothyroidism and androgen metabolism are possible at various links.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗

Hormone serum levels and hormone receptor contents of endometria in women with normal menstrual cycles and patients bearing endometrial carcinoma.

Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (HPRL), 17 beta-estradiol (E2) and progesterone (P) were estimated in 46 subjects with normal menstrual cycles in whom hysterectomies were performed. Estrogen (ER) and progesterone receptor (PgR) levels in endometrial samples of these patients were estimated, and histological dating of the cycle day was carried out. Similarly, hormone serum levels and ER as well as PgR were estimated in 17 patients with endometrial carcinoma. No correlation between LH, FSH, HPRL and ER as well as PgR was noted in the normal subjects. Correlation between P and ER was observed in this group. Parallel variations between E2 and PgR were recorded in the normal females. In the carcinoma group no correlations between hormone serum levels and receptor contents were found, but ER and PgR correlated with each other. Receptor levels was highest in the well-differentiated group of endometrial carcinoma. The present experiments provide a rationale for progestagen therapy of carcinoma of the endometrium.

Endometrium↗

Direct pituitary effects of testosterone and luteinizing hormone-releasing hormone upon follicle-stimulating hormone: analysis by radioimmuno- and radioreceptor assay.

The present studies examine the effects of testosterone (T) and LHRH, alone or in combination, on the amount of FSH secreted by pituitary cells in culture. FSH was quantified by RIA and radioreceptor assay (RRA). Half of the cultures were exposed to T for 3 days. The remainder served as controls. Each of these two groups was divided in half and exposed to medium only or LHRH (10(-8) M) for 4 h. Medium was collected from all cultures after 3 days +/- T (medium 1) and after 4 h +/- LHRH (medium 2). After medium 2 collection, cell homogenates were prepared. In a second study, T-treated cell cultures also received 0, 0.5, or 5.0 micrograms/dish tunicamycin for the last 16 h of the 3-day incubation. During the 3 days of culture, the T-treated group secreted greater amounts of immunoactive FSH than controls. However, LHRH-induced FSH release measured by RIA was blunted as a result of T exposure compared with untreated controls. T treatment elevated intracellular immuno-FSH stores. Each sample was quantitated for FSH activity by RRA, and the FSH RRA/RIA was calculated. T and/or LHRH treatment, while eliciting FSH hypersecretion, caused a reduction in the RRA/RIA of secreted FSH. Changes in the RRA/RIA are thought to occur as a result of alterations in the glycosylation of FSH. To test this hypothesis, T-treated cells were exposed to tunicamycin, a drug that reduces the rate of glycosylation of secreted proteins. Exposure of cells to this drug prevented the reduction in the RRA/RIA of secreted FSH caused by T and/or LHRH. FSH secreted from control, T-treated, or T-treated plus tunicamycin-exposed cells was examined by isoelectric focusing. T-Treated cells released a greater proportion of FSH forms with lower isoelectric points (indicative of a greater degree of glycosylation) compared with controls. Tunicamycin exposure reversed T's effect upon the isoelectric profile. These studies demonstrate a direct pituitary action of LHRH and T upon the type of FSH released. During times of hormonally induced increases in the rate of FSH secretion, the pituitary releases FSH forms that are more heavily glycosylated, exhibit a lower isoelectric point, and show a reduced RRA/RIA. FSH secreted after T treatment would be expected to have an increased plasma half-life due to the protective effects of the sugar residues. Thus, the existing hormonal milieu exerts a multidimensional effect upon FSH released by pituitary cells in culture that cannot be appreciated by RIA assessment alone.

Animals↗

Analysis of computer-generated hydropathy profiles for human glycoprotein and lactogenic hormones.

Analysis of hydrophobic and hydrophilic regions of human lactogenic (PRL, GH, and placental lactogen) and glycoprotein hormones (FSH, LH, TSH, and hCG) by the method of Kyte and Doolittle has been performed. A BASIC program, developed for the IBM personal computer, produces graphical and tabular results. The net hydropathy value, a new parameter based on the Kyte and Doolittle analysis which may be useful for comparing various polypeptides, was developed. This value is correlated with physical properties, such as solubility of the glycoprotein hormones. New (more hydrophilic) indices were assigned for glycosylated asparagine, serine, and threonine residues, and slightly more hydrophilic indices were assigned for half-cystines found in disulfide bonds. The results indicate that the so-called determinant loop of Ward and Moore is hydrophilic (accessible) and suggest that regions on either side of this loop should also be considered as potential effectors of hormone specificity. It is suggested that binding (protein-protein interaction) sites tend to be modestly hydrophilic, but also contain residues that could interact through the hydrophobic effect.

Chemical Phenomena↗

Plasma levels of adrenocorticotropin and cortisol in women receiving oral contraceptive steroid treatment.

The secretion rate and plasma concentration of the adrenocortical steroid cortisol is modified in subjects treated with estrogenic and/or progestational steroids. The effects of contraceptive steroids on the secretion of ACTH are poorly documented, however, In the current investigation, we found that concentrations of ACTH and cortisol in plasma obtained at 0800--0900 h from a group of women with normal cyclic menses (n = 4) ranged from 78--120 pg/ml and 77--137 ng/ml, respectively. Although significant cyclic changes in the plasma levels of LH, FSH, 17 beta-estradiol, and progesterone occurred during the ovarian cycle, no obvious cyclic fluctuations in plasma levels of ACTH or cortisol were observed. In women treated with Norinyl 1 + 80 (1.0 mg norethindrone plus 0.08 mg mestranol), plasma concentrations of LH, FSH, 17 beta-estradiol, and progesterone were significantly lower (P less than 0.001) than plasma levels of these hormones in normal women during the ovarian cycle. The mean daily plasma concentrations of ACTH were significantly lower (P less than 0.001), whereas plasma cortisol levels were significantly higher (P less than 0.001) in women treated with oral contraceptive steroids compared to the levels of these hormones in the untreated ovulatory women.

Adrenocorticotropic Hormone↗

Postpartum return of ovarian activity in nonbreastfeeding women monitored by urinary assays.

Assays of first morning urine samples for pregnanediol-3 alpha-glucuronide (PdG), estradiol-17 beta-glucuronide (E2G), and LH were used to monitor endocrine function in 16 regularly cycling women and 22 postpartum nonbreastfeeding women. Twice weekly blood samples were also obtained from the postpartum group. Ovulation was inferred by a significant rise in LH and PdG, and reversal of the E2G to PdG ratio. Luteal phase PdG excretion was measured by the peak of smoothed PdG levels and the area under the smoothed luteal phase PdG curve. The lower limits of normal established in 16 cycling women were a peak luteal phase PdG of 4 micrograms/ml and an area under the PdG curve of 20 micrograms/ml. In the postpartum women, 32% of first cycles were anovulatory, and among ovulatory cycles, 73% had abnormally low luteal phase PdG excretion or short luteal phases. In second and subsequent cycles, 15% were anovulatory and 26% had luteal phase abnormalities. There was a progressive increase in luteal PdG excretion from the first to third cycles. The mean delay before first ovulation was 45.2 days, and no woman ovulated before 25 days after delivery. The correlations between blood and urinary hormone levels were 0.78 for PdG, 0.65 for E2G, and 0.55 for LH. We conclude that assays of daily early morning urine samples provide reliable information on ovulation and luteal phase adequacy, and that there is gradual recovery of pituitary ovarian function after parturition.

Adult↗

Influence of suckling and of suckling followed by TRH or LH-RH on plasma prolactin, TSH, GH and FSH.

Ten women were studied during the first post-partum week. Suckling for 20 min induced a marked increase in plasma prolactin, reaching a maximum within 0-25 min after the end of suckling and then returning to pre-suckling levels after 120 min. Suckling induced no changes in plasma thyrotrophin (TSH), growth hormone (GH) or follicle stimulating hormone (FSH). The iv injection of 200 mug of thyrotrophin releasing hormone (TRH) immediately after suckling resulted in an additional increase in plasma prolactin and a rise in TSH. When given 120 min after suckling TRH was followed by increased plasma levels of prolactin and TSH, which for both hormones were of a magnitude comparable to the TRH induced increment seen immediately after suckling. Thus, suckling did not inhibit the effect of TRH on the release of TSH. These studies indicate that TRH is probably not involved in the suckling induced increase in prolactin secretion. The mean plasma FSH level was below the limit of detection before and after suckling. Neither plasma FSH nor prolactin showed any appearant changes following the iv injection of 25 mug of luteinizing hormone releasing hormone (LH-RH), when given immediately after and 120 min after suckling. When given after suckling as indicated above, TRH induced no changes in plasma GH or FSH and similarly LH-RH was without influence on plasma GH and TSH.

Adult↗

Urinary hormone analysis as a diagnostic tool to evaluate the ovarian function of female gorillas (Gorilla gorilla).

Daily urine samples were collected from 4 adult female gorillas over 7 menstrual cycles. Urinary oestrone conjugate and pregnanediol-3-glucuronide (PDG) were measured by radioimmunoassay; LH was measured by enzyme immunoassay and each hormone was indexed by creatinine. The quantity of urinary LH during the ovulatory surge was positively correlated with the quantity of PDG excreted during the luteal phase (r = 0.87, P = 0.0013). The observations indicate a relationship between the quality of the LH surge and the levels of PDG in the luteal phase and suggest that both the LH surge and subsequent luteal phase function may be predictable from the oestrogen excretion profile during the follicular phase.

Animals↗

Evidence for the action of bovine follicular fluid factor(s) other than inhibin in suppressing follicular development and delaying oestrus in heifers.

The aim of this study was to investigate the importance of inhibin in the delay in return to oestrus in heifers induced by steroid-stripped bovine follicular fluid (bFF). Oestrous activity was synchronized in 18 Hereford x Friesian heifers with two injections of prostaglandin (PG) 12 days apart. At the time of the second PG injection (time 0), the animals were assigned at random to one of three experimental groups and received i.v. injections of 20 ml saline (controls, n = 6), whole bFF (FF group, n = 6) or bFF in which the bioactive inhibin content had been reduced by > 95% by immunoaffinity chromatography (-INH group, n = 6; inhibin content approximately 0.8 ml whole bFF) every 8 h for 2 days. In a dose-response study, 2.5 ml whole bFF was insufficient to delay oestrus consistently following a similar synchronization regimen. Blood samples were taken every 8 h, initially before each injection and then subsequently for a further 9 days for hormone analysis. Animals were observed every 8 h throughout the experiment for signs of behavioural oestrus. The ovaries of all animals were examined using real-time ultrasonography about 30 h after the second PG injection. Treatment failed to suppress peripheral follicle-stimulating hormone (FSH) concentrations, although a significant increase was observed in both treatment groups after cessation of injections. Progesterone concentrations fell immediately after the second PG injection in all animals and remained below minimum detectable concentrations in all treated animals for the remainder of the experiment. In control animals, progesterone rose above minimum detectable concentrations by day 6 and continued to rise until the end of the experiment. Analysis of samples taken from treated animals several days after observed oestrus revealed that all had apparently ovulated. Mean daily luteinizing hormone (LH) concentrations did not differ between treatment groups before ovulation, but after ovulation, mean daily LH was significantly reduced in control animals as progesterone concentrations rose. Follicular development, as assessed by the mean antral diameter of the largest follicle on a pair of ovaries at ultrasound examination, was significantly suppressed in treated animals compared with controls (P < 0.01) and there was no significant difference (P = 0.397) between the two treatment groups. Control animals displayed oestrus 68 h (+/- 8 SEM) after the second PG injection, but oestrus was delayed in treated animals to 186h +/- 5 (FF group) and 191 h +/- 6 (-INH group).

Analysis of Variance↗

Evaluation of danazol as an oral contraceptive.

The effect of Danazol as an oral contraceptive in doses of 50, 100, and 200 mg daily for 6 months was studied in 3 groups of 10 women. Both 50 and 100 mg Danazol daily were well tolerated, but one pregnancy occurred among the women receiving 50 mg daily, and 2 pregnancies occurred in women receiving 100 mg daily. There were no pregnancies in women taking 200 mg Danazol daily; however, the side effects were frequent and 5 of the 10 patients withdrew from the study prior to 6 months of therapy. Six patients in this study were followed intensively with blood hormone analysis, vaginal cytology, and pathologic evaluation, and these findings are detailed.

Acne Vulgaris↗

[Experimental endocrinological studies in gilts near the time of ovulation using Gn-RH vet. "Berlin Chemistry"].

Knowledge of endocrine processes in pro-oestrus and oestrus in conjunction with physiological alterations is of greatest importance to biotechnological control of follicular maturation and ovulation. Methods of hormonal analysis and ovarian diagnosis were used to check on the effectiveness of Gn-RH vet. "Berlin-Chemie" for induction of the luteinising hormone (LH) peak and ovulation. Release in gilts of LH was found to depend on dosage, after 100, 300, and 900 micrograms Gn-RH had been administered at 3 p.m. on the 4th day after synchronisation of ovulation. LH release and induction of ovulation due to these variants were insufficient in some of the animals. Ovulation was then decisively improved in animals with LH peak by subsequent injection of 300 or 900 micrograms Gn-RH at 8 a.m. on the 5th day. Repetitive injections of 300 micrograms Gn-RH at 8 and 8.45 a.m. on the 5th day did not trigger off increased LH release from the pituitary gland. The Gn-RH effect was substantially improved by use of an absorption-retarding preparation (polystyrene sulphonic acid).

Animals↗

[Therapeutic results with tamoxifen in oligospermia. II. Hormonal analysis and semen parameters].

During a five months lasting treatment with tamoxifen (2 X 10 resp. 2 X 20 mg daily) a significant increase of testosterone, LH, FSH, estradiol, free testosterone and SHBG was found. The prolactin levels diminished. In semen analysis the values of pH and fructose decreased within the normal range. The sperm density increased significantly, but we could not ascertain whether a dosage of 2 X 20 mg/die will provide better therapeutic results. Furthermore the hormonal and seminal investigations described in this paper did not allow to predict those patients who would be good responders on tamoxifen therapy. Tamoxifen seems to be effective in normo-, but also in hypo- and hypergonadotropic patients.

Estradiol↗

[The clinical and hormonal effects of laparoscopic multiple punch resection (MPR) of the ovary in polycystic ovary syndrome].

Eleven women with polycystic ovary syndrome (PCO) were treated with Laparoscopic Multiple Punch Resection (MPR) of the ovarian follicle and capsule and studied by hormone analysis before and after MPR. In 90.9% of the patients, ovulation appeared to occur within 9 weeks and 63.6% conceived within 26 weeks. No changes in serum LH and FSH levels were seen before and after MPR, but testosterone levels which were in the upper normal range or slightly elevated before treatment were reduced after MPR. Endocrine responses to MPR were similar to those described previously after wedge resection. Laparoscopic MPR is a simple and least invasive method and makes it unnecessary to worry about periovarian adhesion after operation. Furthermore, other causes of infertility can be examined by laparoscopy. MPR appeared to be a promising alternative treatment for patients with PCO.

Adult↗