Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transforming growth factor alpha (TGF alpha) inhibits hormone production by cultured follicular cells but evidence of an effect of TGF alpha on ovarian hormone secretion in vivo is still required. Eleven ewes with an autotransplanted ovary received, by ovarian arterial infusion, either 5 micrograms/h recombinant rat TGF alpha (n = 6) or placebo (n = 5) for 12 h on day 10 of the luteal phase. Two hours before the start and 1 hour before the end of the infusion each ewe received a single injection of gonadotrophin-releasing hormone (GnRH; 150 ng i.v.). Two hours after the end of the infusion luteal regression was induced with prostaglandin F2 alpha (PGF2 alpha; 125 micrograms i.m.). Ovarian and jugular venous blood samples were taken at 10-min, 15-min or 4-h intervals from 2 h before the start of the infusion until 96 h after PGF2 alpha and the rates of secretion of ovarian oestradiol, inhibin, progesterone and androstenedione were determined. Jugular venous concentrations of LH and FSH were also measured and follicle populations monitored by real-time ultrasound scanning. Infusion of TGF alpha resulted in a significant (P < 0.05) depression in the amplitude of the pulsatile response of oestradiol and androstenedione secretion to the GnRH-induced LH pulse at the end of the infusion. Ovarian inhibin secretion was acutely suppressed by TGF alpha infusion (P < 0.001) and remained lower than controls for the period of the experiment. Luteal phase progesterone secretion was also acutely inhibited (P < 0.001) by infusion of TGF alpha, and in one treated ewe progesterone secretion was elevated 48-84 h after PGF2 alpha. Jugular venous concentrations of FSH in TGF alpha-treated ewes were significantly (P < 0.001) elevated over controls during the first 48 h of the follicular phase and the LH surge was delayed for about 10 h (P < 0.05). Infusion of TGF alpha caused a marked decline (P < 0.05) in the number of large follicles within 12 h of the end of the infusion. Two of the six treated ewes, including the one with high follicular phase progesterone, had unusually large (8.7 and 10 mm) follicles present from 48-96 h after PGF2 alpha. We conclude that direct arterial infusion of TGF alpha results in acute inhibition of ovarian steroid and inhibin secretion that is associated with induction of atresia in the population of large follicles. The lack of feedback of ovarian hormones results in a rebound increase of FSH which stimulates the growth of more ovarian follicles and the eventual re-establishment of ovarian hormone secretion and normal cyclicity.
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PMID:The effect of ovarian arterial infusion of transforming growth factor alpha on ovarian follicle populations and ovarian hormone secretion in ewes with an autotransplanted ovary. 796 12

1. The sympathetic superior cervical ganglia (SCG) provide innervation to the pineal gland and median eminence through the internal carotid nerve and to the thyroid and parathyroid glands through the external carotid nerve. 2. Postsynaptic activation in median eminence nerve endings shortly after superior cervical ganglionectomy (SCGx) was accompanied by a depression of LH and FSH release and by a 3-5 day delay in rat estrous cyclicity. A decrease in TSH and GH release and an increase in ACTH and prolactin release were also found. These effects were accompanied by a) an increase in medial basal hypothalamic (MBH) LHRH, TRH and GHRH, b) a decrease in MBH somatostatin, AVP and CRH, and c) a normal adenohypophyseal response to hypophysiotropic hormones. Neurohypophyseal AVP release decreased during degeneration of sympathetic nerve terminals in the neurohypophyseal lobe after SCGx. The effects were generally mediated by alpha 1-adrenoceptors and were pineal gland. 3. In thyroid and parathyroid tissue the following events were observed during the wallerian degeneration phase after SCGx: a) alpha 1-adrenoceptor inhibition of thyroxine (T4) release, b) alpha 1-adrenoceptor inhibition, together with beta-adrenoceptor stimulation, of calcitonin release, and c) alpha 1-adrenoceptor inhibition of parathyroid hormone release. Thyroid sympathetic nerves also modulate slow phenomena such as compensatory thyroid growth after partial thyroidectomy. 4. In rats subjected to cholinergic decentralization of the thyroid gland, a decrease of plasma T4 and an increase of plasma TSH, as well as an impaired goitrogenic and thyroid compensatory response were detectable. The calcitonin and PTH response to changes in calcium levels increased after regional parasympathetic denervation. 5. The results indicate that cervical autonomic nerves constitute a parallel pathway through which the brain communicates with the endocrine system.
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PMID:Peripheral neuroendocrinology of the cervical autonomic nervous system. 808 Dec 83

The differential regulation of immunoactive FSH and LH secretion by endogenous LH-RH was studied using LH-RH antagonists (Ac-D-Trp1,2, D-Cpa2, D-Lys6, D-Ala10LH-RH (MI-1544) and (Ac-D-Nal1, D-Phe(pCl2), D- Trp3, D-Cit6, D-Ala10LH-RH (SB-030) in ovariectomized (OVX) and regularly cycling rats. Single injections of 10 micrograms and 100 micrograms doses and long-term treatment with 10 micrograms doses of MI-1544 were used in OVX animals. Serum and pituitary LH and FSH, as well as serum estradiol and progesterone was determined by RIA during and/or after the treatment. Single injections of MI-1544 in OVX animals caused prompt (in 2 h) and long-lasting (for more than 24 h) suppression of the serum LH, while no or late decrease (after more than 6 h) of the serum FSH. Long-term treatment with the same analog decreased the serum LH (by 50%) and moderately increased the pituitary LH (by 21%) but did not change the serum and the pituitary FSH concentrations. In normal rats, long-term treatment with both of our analogs also resulted in divergent alterations in the LH and FSH concentrations. Serum LH dropped to undetectable levels,while serum FSH did not change significantly. Pituitary LH increased (by 31 to 41%), while FSH decreased (by 27 to 38%). Marked depression was found in the serum progesterone (by 64%) but no significant change in the serum estradiol levels, after the long-term treatment for 21 days. The ovarian cycles were interrupted, and no ovulation appeared during the treatment. Significant decrease was detectable in the weight of the ovaries (by 46%), whereas the weight of the uteri did not change or slightly elevated (by 22%), after the treatment with SB-030 or MI-1544, respectively.
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PMID:Antiovulatory doses of antagonists of LH-RH inhibit LH and progesterone but not FSH and estradiol release. 868 Apr 31

Recombinant human inhibin A (rhInh) or steroid-free bovine follicular fluid (bFF) were infused into the ovarian artery of anoestrous ewes with ovarian autotransplants induced to ovulate with a pulsatile regimen of GnRH applied after a 10-day pretreatment with progestagen sponges. In the period 12-24 h after sponge withdrawal ewes received ovarian arterial infusions of saline (n = 6), 0.3 micrograms rhInh/h (n = 5), 1.6 micrograms rhInh/h (n = 5) or 25 microliters bFF/h (n = 4). Controls had a normal follicular phase with an LH surge 43 +/- 3 h after sponge withdrawal which resulted in ovulation (six out of six). Both doses of rhInh increased ovarian venous inhibin concentrations in a dose-related fashion (P < 0.05) but resulted in depressions (P < 0.05) in FSH concentrations of similar magnitude. Both doses of rhInh acutely inhibited ovarian oestradiol and androstenedione secretion (P < 0.01) but at the end of rhInh infusion oestradiol secretion was quickly re-established without a corresponding increase in FSH. LH surges were detected in five out of five and three out of five ewes infused with low and high doses of rhInh respectively, and progesterone concentrations during the subsequent luteal phase were depressed (P < 0.05). Infusion of bFF had no effect on inhibin or FSH concentrations but resulted in acute inhibition (P < 0.01) of ovarian oestradiol, androstenedione and inhibin secretion, a delay (P < 0.05) in the time to the LH surge and a depression (P < 0.05) in luteal-phase progesterone concentrations. In conclusion, while the depression in FSH induced by rhInh cannot be excluded as a cause for the inhibitory effects of rhInh treatment on ovarian function, such a mechanism cannot fully explain the ovarian responses obtained to rhInh infusion. These results therefore support a direct ovarian role for inhibin in the modulation of ovarian function in addition to its indirect role in controlling FSH. This conclusion is supported by the demonstration that bFF can induce similar inhibitory effects on ovarian function without changing FSH.
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PMID:The effect of ovarian arterial infusion of human recombinant inhibin and bovine follicular fluid on ovarian hormone secretion by ewes with an autotransplanted ovary. 869 Nov 12

The present study was designed to assess the relationship between puerperal hormonal changes and mood. Twenty-five postpartum physically and mentally healthy, drug-free women were included in the study; seven later dropped out. Blood samples 'were drawn between 8 and 9 a.m. just prior to delivery, and again three days after delivery, before discharge. Blood levels of LH TSH, FSH, estrogen and prolactin were determined. Three days after delivery, a psychiatric interview was conducted during which psychometric rating scales (Brief Psychiatric Rating Scale, Hamilton Depression and Hamilton Anxiety Rating Scales, and Beck Depression Inventory) were completed. The rate of change in hormonal blood levels was analyzed in relation to the scores on the rating scales. Results showed that the rise in prolactin plasma levels had a negative and significant correlation with the scores on the Hamilton anxiety scale. This may indicate that high prolactin plasma levels, associated with milk production, may lead to lower anxiety levels in lactating women.
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PMID:Mood and hormonal changes during late pregnancy and puerperium. 877 88

The effect of pretreatment with the gonadotropin releasing hormone (GnRH) agonist D-Trp6-LHRH (Decapeptyl) on platelet serotonin transporter in women undergoing assisted reproductive treatment (ART) was investigated and compared with women treated with human menopausal gonadotropin (Pergonal). The study group (n = 10) was exposed for 12 days to 3.2 mg Decapeptyl C.R. while a comparison group (n = 9) was exposed to 11 days of human meno-pausal gonadotropin (Pergonal). All patients were assessed with the Hamilton depression and anxiety scales before and after treatment, and platelet and plasma samples were collected at the same time points. Plasma levels of estradiol, progesterone. FSH and LH were determined by radioimmunoassay (RIA). Platelet serotonin transporter was labeled using high affinity [3H]imipramine binding. The GnRH analogue induced ovarian suppression as reflected by low plasma estradiol levels, while Pergonal administration induced ovarian stimulation. An elevation in the Hamilton depression and anxiety scale scores was observed in the Decapeptyl treated group; this mood alteration was associated with a significant decrease (19%, P < 0.05) in the density (Bmax) of platelet [3H]imipramine binding sites. No significant change was observed in the Bmax of the Pergonal treated group. These results indicate that ovarian suppression (menopausal-like state) in young women is associated with depressed and anxious mood and decreased serotonin transporter density.
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PMID:Chronic GnRH agonist administration down-regulates platelet serotonin transporter in women undergoing assisted reproductive treatment. 878 88

Follicles were monitored daily by ultrasound and blood samples for FSH assay were collected daily from eight heifers from day 90 of pregnancy to the emergence of the first postpartum follicular wave. Follicles > or = 6 mm in diameter emerged in groups or waves in each heifer (P < 0.005). Follicular waves developed rhythmically throughout pregnancy, except that follicles > or = 6 mm were not detected during the last 21.6 +/- 2.4 (mean +/- SEM) days of pregnancy. The characteristics of the first follicular wave after day 90 were similar to previous reports for days 10-100. However, between months 4 (days 90-119) and 5, there was a decrease (P < 0.05) in monthly means for maximum diameter (mm) of largest (21.1 +/- 0.5 versus 9.5 +/- 0.5) and second largest (8.0 +/- 0.3 versus 6.9 +/- 0.2) follicles, duration of the interwave interval (8.1 +/- 0.4 versus 6.6 +/- 0.3 days), and number of follicles per wave (3.7 +/- 0.4 versus 2.5 +/- 0.4). Averaged over all follicular waves during months 4-9, the concentrations of FSH normalized to the emergence of a follicular wave increased (P < 0.05) over the 3 days before emergence, reached peak values on the day of emergence of the future dominant follicle at 4 mm, and decreased (P < 0.05) over the 3 days following emergence. Surges in FSH concentrations occurred throughout pregnancy, but during the last 30 days of pregnancy the number of surges was reduced and each heifer had one or two ineffective surges (no follicular wave detected). The temporal relationship between FSH surges and emergence of waves was closer (P < 0.01) than would be expected if the two events were independent. Surges of FSH occurred rhythmically even when there was no follicular response (no follicle > 5 mm). In association with waves in which the largest follicle reached > or = 10 mm compared with 6-9 mm, there was greater depression in the FSH nadir, longer intervals from FSH peak to nadir, and longer intervals between adjacent FSH peaks and adjacent waves.
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PMID:Relationships between FSH and ovarian follicular waves during the last six months of pregnancy in cattle. 903 86

Raised activity of the LH axis caused by activating mutations of LH receptor gene presents with precocious puberty in boys, analogous to the presentation of LH secreting pituitary adenomas (Faggiano et al., 1983; Ambrosi et al., 1990). LH "hyperactivity' in females appears to have no effect. Hyperactivity of the FSH axis caused by activating mutations of the FSH receptor gene might parallel the presentation of FSH secreting pituitary adenomas with Sertoli cell hypertrophy in men (Heseltine et al., 1989) or reversible premature ovarian failure in women (Moses et al., 1986; Okuda et al., 1989). Indeed the first such case to be described is a male who maintained testicular volume and fertility in the absence of gonadotrophins (Gromoll et al., 1996). Female precocious puberty may require hyperactivity of both gonadotrophin axes because of the "two-cell' arrangement required for ovarian oestrogen production. Mutations of the Gs alpha-subunit gene can mimic this situation in some women with the McCune-Albright syndrome (Malchoff et al., 1994). Lack of LH activity caused by defects in the LH beta molecule causes infertility in men and that resulting from inactivating mutations of the LH receptor gene causes Leydig cell agenesis in men while ovarian development in females is relatively normal. Lack of FSH activity caused by defects in the FSH beta caused infertility in a female, and that caused by inactivating mutations of the FSH receptor gene causes ovarian dysgenesis in women but only variable depression of spermatogenesis in men. Incidentally, this categorization of reproductive disorders may also be applied to the TSH axis. Pituitary adenomas and activating mutations of the TSH receptor gene (Parma et al., 1993) cause hyperthyroidism and TSH beta gene defects (Hayashizaki et al., 1989) and inactivating mutations of the TSH receptor gene (Sunthornthepvarakul et al., 1995) cause hypothyroidism. To complete the analogy with thyroid disorders, it is curious that despite structural similarities with the TSH receptor, neither LH nor FSH receptor autoantibodies have a prominent role in ovarian pathophysiology (Moncayo et al., 1989; Van Weissenbruch et al., 1991; Simoni et al., 1993). Complete gonadotrophin resistance is likely to be very rare, however, so what are we likely to find in partial gonadotrophin resistance? Might the "resistant ovary syndrome' come right in the end, with corresponding minor FSH receptor mutations? Experience with insulin and androgen resistance syndromes suggests that such a scenario is unlikely. Insulin receptor gene mutations are found in extreme Type A insulin resistance but not in moderate forms of insulin resistance (O'Rahilly et al., 1991). Androgen receptor gene mutations are found in nearly all cases of complete androgen insensitivity but rarely in partial forms (Patterson et al., 1994). Mild resistance to hormone action is rarely detectable in relatives who are heterozygous for receptor mutations which are inherited in a recessive pattern. It seems unlikely therefore, that individuals heterozygous for inactivating receptor mutations will manifest symptoms of reproductive disorders and account for common conditions. Thus, while mutation analysis provides new insights into the gender specific role of the gonadotrophins the cause of early gonadal failure in the majority of individuals remains a mystery.
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PMID:Clinical manifestations of genetic defects affecting gonadotrophins and their receptors. 903 30

Although the GnRH agonist analogs have become an established treatment for precocious puberty, there have been few long term studies of reproductive function and general health after discontinuation of therapy. To this end, we compared peak LH and FSH after 100 microg sc GnRH, estradiol, mean ovarian volume (MOV), age of onset and frequency of menses, body mass (BMI), and incidence of neurological and psychiatric problems in 2 groups of girls: those with precocious puberty due to hypothalamic hamartoma (HH; n 18) and those with idiopathic precocious puberty (IPP; n = 32) who had been treated with deslorelin (4-8 microg/kg x day, s.c.) or histrelin (10 microg/kg x day, s.c.) for 3.1-10.3 yr and were observed at 1, 2, 3, and 4-5 yr after discontinuation of treatment. The endocrine findings were also compared to those in 14 normal perimenarcheal girls. There were no differences between the HH and IPP groups in age or bone age at the start of treatment, at the end of treatment, or during GnRH analog therapy. We found that whereas the peak LH level was higher in HH than in IPP girls before (165.5 +/- 129 vs. 97.5 +/- 55.7; P < 0.02) and at the end (6.8 +/- 6.0 vs. 3.9 +/- 1.8 mIU/mL; P < 0.05) of therapy, this difference did not persist at any of the posttherapy time points. LH, FSH, and estradiol rose into the pubertal range by 1 yr posttherapy in both HH and IPP. However, the mean posttherapy peak LH levels in both HH and IPP groups tended to be lower than normal, whereas the peak FSH levels were not different from normal, so that the overall posttherapy LH/FSH ratio was decreased compared to that in the normal girls (HH, 2.7 +/- 0.3; IPP, 2.6 +/- 0.1; normal, 5.2 +/- 4.8; P < 0.05). The MOV was larger in HH than IPP at the end of treatment (3.7 +/- 3.5 vs. 2.0 +/- 1.2 mL; P < 0.05) and tended to increase in both groups over time to become larger than that in normal girls by 4-5 yr posttherapy (HH, 14.9 +/- 12.9; IPP, 7.6 +/- 2.2; normal, 5.4 +/- 2.5 mL; P < 0.05). Whereas the onset of spontaneous menses varied widely in both groups, once menses had started, the HH group had a higher incidence of oligomenorrhea. Pelvic ultrasonography revealed more than 10-mm hypoechoic regions in 4 HH patients, 15 IPP patients, and 3 normal girls, all of whom were reporting regular menses. Live births of normal infants were reported by 2 HH and 2 IPP patients, and elective terminations of pregnancy were reported by 1 HH and 2 IPP patients. BMI was greater than normal in HH and IPP both before treatment and at all posttherapy time points and tended to be higher in the HH patients. Marked obesity (BMI, +2 to +5.2 SD score) was observed in 5 HH and 6 IPP patients, 1 of whom had a BMI of +2.5 SD score and developed acanthosis nigricans, insulin resistance, and hyperglycemia. Seizure disorders developed during GnRH analog therapy in 5 HH and 1 IPP patient, and 2 additional HH girls developed severe depression and emotional lability posttherapy. Although the mean anterior-posterior dimension of the hamartoma was larger in the HH patients with seizure than in those who were seizure free (1.7 +/- 1.2 vs. 0.9 +/- 0.4 cm; P < 0.05), no change in hamartoma size was observed either during or after therapy, and no patient has reported the onset of a seizure disorder posttherapy. Other than a tendency toward a larger MOV, a higher incidence of oligomenorrhea, obesity, and frequency of neurological disorders, recovery of the reproductive axis after GnRH analog therapy was not markedly different in HH compared to IPP. Continued follow-up of these patients may determine whether the decreased LH responses and increased BMI in both groups compared to those in normal girls remain clinically significant problems.
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PMID:Reproductive axis after discontinuation of gonadotropin-releasing hormone analog treatment of girls with precocious puberty: long term follow-up comparing girls with hypothalamic hamartoma to those with idiopathic precocious puberty. 992 60

GnRH agonist (GnRHa) administered for 6 months leads to an effective desensitisation of the pituitary and hypoestrogenism without exerting a particular effect on the whole metabolism. At the end of the first month's a suppression of the serum estradiol levels are achieved, the level of LH and FSH decline in the hypogonadotropic range. No negative influence on the lipid metabolism after administration of GnRH agonist has been observed. The balance of HDL/LDL does not change during the treatment. There were neither any negative changes in the liver metabolism, kidney function nor in the electrolyte values. In anaemic premenopausal women, for example due to serious menstrual problems, a normalisation of the haemoglobin concentration is obtainable already after a 12-week treatment. With regard to the hemostatis system a significant reduction of the procoagulant activity, fibrin turnover rate and a significant improvement of fibrinolytic activity can be observed under a GnRHa therapy. Although the use of GnRHa leads without doubt to a drastic reduction in the uterus blood flow there are no signs that this also leads to a change in the cerebral arteries blood flow. Menstrual bleeding occurs on average 3 months after the last injection of an GnRHa depot injection; with daily injection or nasal spray 3 to 4 weeks earlier. Theoretical considerations as well as the world-wide use as part of the infertility treatment--in some countries more than 90% of all IVF-cycles are performed using GnRH--,contradict the fact that GnRHa cause a teratogenic effect. Domineering undesirable side-effects during a treatment with GnRH can be traced back almost exclusively to the effective hormonal deprivation. In this context it is remarkable which percentage patients complain about trouble of this spectrum before GnRHa treatment is initiated. The chronicle reduction of the sexual hormone level leads without a doubt to a reduction of bone mineral density. The clinical relevance is furthermore a matter of controversial discussion. Prevention measures can be undertaken through an add-back therapy. This can also be of help in the case of vegetative side-effects caused by a decrease in sexual hormones. The question arises to what extent effective non hormonal add-back therapies are at disposal in the treatment of sexual hormone related malignant tumours. Also men with testosterone deprivation can suffer from distinctive hot flushes, sleeping disturbances and depression which requires some kind of relief in order to maintain an acceptable quality of life.
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PMID:[In Process Citation] 1046 91


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