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)

In young, adult male volunteers Leydig cell function tests were performed consisting of i.m. administration of 1500, 3000 or 4500 IU of HCG on days 1, 2 and 3 and plasma testosterone determination by radioimmunoassay. The stimulatory effect of HCG known from the literature is reconfirmed. However, no difference between the effect of the three dosage levels was found and the first significant effect of HCG was observed 24 h after its first application. Testosterone levels on day 3 and 4 are higher but not different from each other. A depression of plasma testosterone after treatment with an anabolic steroid (1alpha, 17alpha-dimethyl-5alpha-androstan-17-ol-3-one) 20 mg daily for 14 days is described. Reactivity to HCG was sustained in these subjects, but testosterone response to HCG was diminished at all investigated time intervals.
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PMID:Plasma testosterone response to HCG in normal men without and after administration of anabolic drug. 87 Mar 13

In vivo assessment of toxicant action on Leydig cell function is subject to homeostatic mechanisms which make it difficult to determine whether any changes seen in serum testosterone (T) concentration are due to extragonadal endocrine alterations or to a direct effect on the Leydig cell. For example, metal cations administered in vivo have been shown to depress serum T concentration and alter serum concentrations of pituitary hormones in laboratory animals. The studies reported here use a testicular cell culture technique to evaluate Leydig cell testosterone biosynthesis in the presence of several metal cations. To determine the site of toxic action, the Leydig cells were stimulated to produce testosterone by using human chorionic gonadotrophin (hCG), dibutyl cyclic adenosine monophosphate (db-cAMP), or several substrates required for the biosynthesis of testosterone. hCG was chosen because resultant T production requires an intact membrane receptor and db-cAMP was used to test for post LH receptor defects caused by the metals. The other substrates were chosen to isolate the effect of metals on enzymatic pathways. Collagenase dispersed testicular cells (15% Leydig cells) were incubated with metal cations (1 to 5000 microM) for 3 hr in the absence and presence of maximally stimulating concentrations of hCG, db-cAMP, 20 alpha-hydroxycholesterol (HCHOL), or pregnenolone (PREG), and T concentration was determined by radioimmunoassay. In one separate experiment we also tested the effect of the substrates progesterone, 17 alpha-hydroxy-progesterone, and androstenedione on Cd2(+)-treated Leydig cells. The results show no change in Leydig cell viability with any metal cation treatment during the 3-hr incubation. Ca2+, Cr3+, Fe3+, Mg2+, Na+, or Pb2+ had no effect on stimulated testosterone. Dose-response depression in both hCG- and db-cAMP-stimulated T production were seen with Cd2+, Co2+, Cu2+, Hg2+, Ni2+, and Zn2+ treatment. Surprisingly, Cd2+, Co2+, Ni2+, and Zn2+, which caused a depression in hCG- and db-cAMP-stimulated T production, caused significant increases in HCHOL- and PREG-stimulated T production over untreated and similarly stimulated cultures. This indicates that these cations may act at multiple sites within the Leydig cell.
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PMID:Effect of cadmium and other metal cations on in vitro Leydig cell testosterone production. 185 Jan 71

Previously we had shown that cis-platinum decreases testosterone levels in rat serum and that hCG reverses this effect. The purpose of these studies was to determine the biochemical basis of cis-platinum-mediated effects on testicular testosterone production. In the testis of rats treated with cis-platinum (7 mg/kg, iv), the mitochondrial P-450scc concentration and side-chain cleavage activity were depressed by 40%. Also, the microsomal 17 alpha-hydroxylase activity and cytochrome P-450 concentration were decreased. Testicular binding capacity (in vitro) for [125I]hCG was decreased by 75-80%. On the other hand, FSH binding to Sertoli cell membrane receptors was not appreciably changed. hCG (25 IU/100 g daily) in treated rats caused complete occupancy of the remaining 20-25% LH receptors and caused a 20- to 30-fold increase in serum and testicular testosterone, a 2-fold increase in mitochondrial P-450scc, and a 5-fold acceleration of side-chain cleavage activity. 17 alpha-Hydroxylase activity and microsomal cytochrome P-450 were not increased over the control values. In addition to testicular functions, pituitary glycoprotein hormone production was assessed. Treatment of rats with cis-platinum (7 mg/kg, iv) did not change serum LH or FSH, but caused a 50% decrease in serum and testicular testosterone levels. A GnRH challenge test (1.5 micrograms/100 g, in 30 min) of treated rats caused prompt increases of 10- to 15-fold in serum LH and resulted in increases in serum and testicular testosterone. Thus, there was little evidence for cis-platinum effects at the level of hypothalamus or pituitary that could account for the decreased testosterone production. Reversal of the cis-platinum effect on steroidogenesis by hCG or GnRH appears to be due to the induction of suprasaturating levels of LH with full occupancy of remaining Leydig cell LH receptors. This, in turn, would reverse the diminished levels of mitochondrial side-chain cleavage activity and cytochrome P-450scc. These data suggest that cis-platinum causes a depression in serum testosterone, mainly by decreasing the number of LH receptors and inhibiting side-chain cleavage activity.
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PMID:cis-platinum-mediated decrease in serum testosterone is associated with depression of luteinizing hormone receptors and cytochrome P-450scc in rat testis. 210 85

Long-Evans rat pups were dosed orally from birth to 21 d with particulate Mn3O4 to obtain a daily dose of 0, 71, or 214 micrograms Mn/body weight . d. Assessments of the hypothalamic, pituitary, or testicular functions were determined by measuring the endogenous or stimulated serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and/or testosterone (T) at 21 or 28 d of age. Body, testes, and seminal vesicles weight and tissue concentrations of Mn were also evaluated. Only slight Mn treatment effects were seen in body and testes weights. No effects were seen either on unstimulated or stimulated FSH or LH serum concentrations. Although no Mn treatment effects were seen on endogenous or 2 h human chorionic gonadotropin (hCG) stimulate serum T concentrations, there was a reduction in the serum T following 7 d of hCG stimulation. The hypothalamic Mn concentrations in animals with these reproductive effects were three times those where alterations in the dopaminergic pathway have been reported. However, no indication of hypothalamic or pituitary malfunction was found. These results suggest that the site of Mn damage that causes depression of sustained serum T concentration is in the testicular Leydig cell.
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PMID:Assessment of the male reproductive system in the preweanling rat following Mn3O4 exposure. 392 53

Morphologic changes in the male reproductive system of mongrel dogs immunized against LHRH were quantitated using linear measurements and morphometric techniques at the light-microscopic level. Two experimental groups (5 nonimmunized control animals and 5 actively immunized animals) were killed 12 weeks after the primary immunization. No significant differences were observed between three immunized dogs having low LHRH antibody titers (immunized-unaffected) and the five nonimmunized control dogs. The two immunized dogs (affected) with the highest antibody titers against LHRH were characterized by atrophy and dedifferentiation of the testes, prostate, and excurrent ducts. The morphologic changes in the testes of these two dogs were striking and included an apparent arrest or significant reduction in the spermatogenic process, concurrent epithelial degeneration, and apparent diminution of Leydig cell mass. Drastic reductions in the size of the prostatic acini and epithelial cells, as well as loss of secretory granules, reflected depression of function and androgen production. Similarly, in the excurrent ducts decreases in the measured parameters and loss of regional cytoplasmic specialization denoted functional decrescence. This study demonstrates the regressive effects of LHRH immunoneutralization on the morphology of the reproductive system in the male dog and further supports the feasibility of this system as an animal model for the study of isolated gonadotropin deficiency.
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PMID:Animal model of isolated gonadotropin deficiency. II. Morphologic responses to LHRH immunoneutralization. 641 70

In patients treated for prostatic carcinoma with oestrogen, orchiectomy or external radiation, serum concentrations of testosterone, LH, FSH, prolactin, TeBG and oestradiol-17 beta as well as changes in sexual behaviour and mental mood were studied. Oestrogen treatment as well as orchiectomy reduced serum testosterone concentration to similar values. Neither totally nor subcapsularly orchiectomized patients responded to HCG stimulation. The free testosterone was 68% lower in oestrogen treated than in orchiectomized patients, probably due to a high TeBG concentration induced by oestrogens. patients oestrogen treated for less than 3 years and in whom the treatment had been withdrawn had normal serum testosterone and LH at follow-up. In contrast, low serum testosterone concentration and normal LH were found after oestrogen cessation in patients oestrogen treated for more than 3 years indicating reduced Leydig cell, and/or hypothalamic-hypophyseal function. In patients oestrogen treated for more than 3 years the serum testosterone concentration neither increased after oestrogen cessation nor decreased after orchiectomy. Absorbed testes doses during radiation treatment were measured from a few to more than 10 Gy but were reduced by about 50% if the gonads were protected by lead shields during anterior and posterior treatment sessions. Radiation may affect gonadal function as decreased serum testosterone concentration and increased LH, FSH were found after treatment. Sexual function was altered after oestrogen, orchiectomy and radiation treatment. Sexual activity and capability were distinctly better maintained after radiation than after orchiectomy or oestrogen treatment. Sixty-seven percent of the patients had coitus or masturbated after radiation treatment, all experiencing orgasm. Patients on oestrogen treatment or after orchiectomy had coitus/masturbation less often (17% in both groups). They also experienced orgasm less often (8% and 17% respectively). The group of patients on oestrogen treatment had a higher average score for depression than those treated with orchiectomy or radiation treatment.
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PMID:Some effects of orchiectomy, oestrogen treatment and radiation therapy in patients with prostatic carcinoma. 642 40

In distinction to the course of reproductive ageing in women, men do not experience a rapid decline of Leydig cell function or irreversible arrest of reproductive capacity in old age. Hence, strictu sensu, the andropause does not exist. Nevertheless, both spermatogenesis and fertility as well as Leydig cell function do decline with age, as shown by a decrease of +/- 35% of total and of 50% of free testosterone levels between the age of 20 and 80 years. The origin of this decline of Leydig cell function resides on the one hand in the testes, and is essentially characterized by a decreased number of Leydig (and Sertoli) cells and on the other hand in the hypothalamo-pituitary complex characterized by a decreased luteinzing hormone (LH) pulse amplitude, LH pulse frequency being maintained. As the responsiveness of the gonadotrophs to gonadotropin-releasing hormone (GnRH) remains unimpaired, one may assume that the amount of GnRH released at each pulse is also reduced, possibly as the consequence of a reduction of the cellular mass of GnRH neurones. Plasma levels of testosterone below the lower normal limit occur, however, only in a minority of elderly men from 7% in the age group 40-60, to 20% in the age group 60-80 and 35% in the age group over 80 years old. Factors influencing testosterone levels in elderly men are multiple: hereditary, environmental (obesity, stress), psychosocial (depression, smoking, drugs) or socioeconomical (diet, hygiene). Whether these elderly men should be substituted with androgens remains controversial.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ageing of the hypothalamo-pituitary-testicular axis in men. 772 Dec 58

The incidence of testicular tumours in dogs is higher than in other species. The main three types are: Sertoli cell tumour, seminoma, and Leydig cell tumour. Metastases are rare. Sertoli cell tumours, and to a lesser extent Leydig cell tumours, are often associated with feminization, which occurs in 19% and 5% of cases, respectively. Seminomas are rarely associated with feminization. Feminization seems to be the result of an excessive oestrogen production by the tumour. In severe cases this may lead to bone marrow depression. Atrophy of the contralateral testis is a common finding. It is not clear whether this is a result of feminization or of age because most tumours occur in older dogs. By investigating the morphology of the testis, and the endocrinological and fertility status of the dog this phenomena is hopefully going to be explained. Extra attention is given to the pathogenesis of feminization.
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PMID:[Testicular tumors in dogs: a literature review]. 861 21

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

The hypothesis that induction of chronic peritoneal sepsis would produce depression of serum testosterone due to a decrease in Leydig cell steroidogenic acute regulatory (StAR) protein or P450c17 steroidogenic enzyme was tested. Male Sprague-Dawley rats (350-400 g) were randomized to septic and nonseptic groups. Sepsis was induced with a cecal slurry (200 mg/kg in 5 mL of 5% dextrose in water (D5W); intraperitoneal) while nonseptic rats received only sterile D5W. Animals (n = 6, in each group) were killed by CO2 asphyxiation and blood samples were collected by direct cardiac puncture at 24 h after induction of sepsis/sham sepsis. The serum concentration of corticosterone, progesterone, estradiol, and testosterone was determined using radioimmunoassay. Western blot analysis was utilized to quantify Leydig cell StAR protein and P450c17 enzyme. Sepsis produced a significant decrease in the serum concentration of testosterone, a down-regulation of StAR protein, and an increase in serum estradiol 24 h after induction of sepsis (as compared with the nonseptic group). Protein levels of P450c17 in Leydig cells and serum concentrations of progesterone and corticosterone 24 h after induction of sham sepsis or sepsis were not different. It is concluded that the decreases in serum testosterone after 24 h of chronic peritoneal sepsis correlated with reductions in StAR protein.
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PMID:Sepsis produces depression of testosterone and steroidogenic acute regulatory (StAR) protein. 1022 Mar 9


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