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Biomedical subjects

L J Gooren

Publications and source records attributed to L J Gooren.

121 records · Page 7Linked to original sources
PubMed1985

Effects of short- and long-term administration of tamoxifen on hCG-induced testicular steroidogenesis in man: no evidence for an oestradiol-induced steroidogenic lesion.

hCG-induced testicular desensitization is characterized by inhibition at the level of the C-17,20-lyase enzyme. This defect has been attributed to an early rise in oestradiol (E2) following hCG administration. To test this hypothesis the E2-receptor antagonist, tamoxifen, was employed. From in vitro studies the evidence suggests that tamoxifen depletes the E2-receptor within 24 h. In this in vivo study, short-term (36 h) administration of tamoxifen (to 6 eugonadal men) did not affect basal plasma levels of LH, FSH, 17 alpha-hydroxyprogesterone (17-OHP), testosterone (T) and E2, whereas long-term (3 months) tamoxifen with treatment of 6 normogonadotrophic oligozoospermic men increased LH and T levels, indicating a biological effect of tamoxifen. The response of 17-OHP, T, E2 and the 17-OHP/T ratio to hCG was similar in short-term and long-term tamoxifen-treated men as well as in 6 untreated eugonadal male controls. These results do not suggest a role for endogenous E2 in the hCG-induced testicular steroidogenic block.

Adult↗
PubMed1984

Estrogen positive feedback on LH secretion in transsexuality.

In order to test the hypothesis whether there is variation in hormonal levels or response to hormonal manipulation that could permit a distinction between heterosexuals and transsexuals, we designed the following protocol: Six male-to-female (m-to-f) transsexuals, six heterosexual control females and six female-to-male (f-to-m) transsexuals were given estradiol benzoate (E2B) (4.5 micrograms/kg/12 hr) for five days. In the female population, E2B treatment was initiated on day 5 of the menstrual cycle. In all the subjects blood luteinizing hormone (LH) and follicle stimulating hormone (FSH), estradiol-17 beta (E2) and testosterone (T) levels were measured twice daily. Additionally, LH and FSH responses to LHRH (100 micrograms iv) stimulation prior to and on day 5 of the E2B treatment were evaluated. In the m-to-f transsexuals, T levels decreased sharply and progressively during estrogen treatment, along with a fall in LH and FSH levels. The magnitude of the LH and FSH responses to LHRH stimulation also decreased following estrogen administration. In the heterosexual female controls and in the f-to-m transsexuals, estrogen administration increased LH levels to a minimum of 100% above initial values from day 3 onwards. Interestingly, the magnitude of the LH increase in the f-to-m transsexuals was greater than that of the heterosexual female controls. In both groups, LHRH stimulation resulted in a greater LH response compared to that prior to estrogen treatment. Our present observations, based on blood hormonal levels and responses to hormonal manipulations do not permit a distinction between heterosexual females and f-to-m transsexuals. There was no convincing evidence for the existence of a positive estrogen feedback on LH secretion in m-to-f transsexuals. These results contradict some of the reported hypotheses concerning hormonal alterations in these individuals.

Adolescent↗
PubMed1984

The effect of endogenous and exogenous gonadotrophin-releasing hormone on the prolactin response to TRH.

The prolactin response to TRH in a group of patients with Kallmann's syndrome was found to be significantly lower compared to a group of hypergonadotrophic hypogonadal patients. Since levels of testicular products are comparably low in both groups, we hypothesize that high endogenous LHRH production might be associated with an increased prolactin response to TRH. In support of this, we were, indeed, able to establish a positive correlation between the magnitude of the prolactin response to TRH and basal and LHRH-stimulated LH/FSH levels (the latter serving as an index of endogenous LHRH production) in: (1) eugonadal men, (2) men with Kallmann's syndrome, (3) oestrogen-treated agonadal men, (4) men with severely impaired spermatogenesis and, (5) agonadal men. A direct relation between LHRH and the prolactin response to TRH was demonstrated in a group of eugonadal men, the prolactin response to TRH being greater after prolonged LHRH pretreatment. We speculate that an increase of endogenous or exogenous LHRH might be associated with decreased hypothalamic dopamine secretion which could directly increase prolactin synthesis. Indirectly, decreased dopamine secretion could augment the potency of TRH in releasing prolactin.

Adult↗
PubMed1984

Prolactin secretion in the human male is increased by endogenous oestrogens and decreased by exogenous/endogenous androgens.

There is evidence that prolactin may be involved in testicular steroidogenesis, and we have therefore investigated whether there is feedback regulation of androgens/oestrogens on prolactin secretion in the human male. To assess this we have measured basal and TRH-stimulated prolactin levels in: Six eugonadal men before and after 2 weeks' administration of the aromatase inhibitor delta'-testolactone, which led to a fall in oestradiol levels with unchanged levels of testosterone. In these patients, prolactin levels decreased. Six eugonadal subjects before and after 6 weeks' administration of dihydrotestosterone undecanoate. In these subjects, prolactin levels decreased. Six agonadal subjects, tested after 12 weeks' treatment with dihydrotestosterone undecanoate and compared to: Six agonadal subjects who received no sex steroid treatment. Again, it was found that dihydrotestosterone treatment decreased prolactin levels in patients from Group C. Six eugonadal subjects were also studied before and after 6 weeks' administration of the androgen receptor antagonist, spironolactone, and this treatment increased Prl secretion. It is concluded that in the human male, endogenous oestrogens increase prolactin secretion whilst exogenous/endogenous androgens decrease prolactin secretion.

Adult↗
PubMed1984

Haemodialysis and testicular function.

Gonadal dysfunction in men with chronic renal failure is well established. However, the effect of haemodialysis on the function of the testis has not been studied in detail, so we have investigated the effect of haemodialysis by measuring the plasma levels of testosterone and dihydrotestosterone, SHBG binding capacity and salivary levels of testosterone. Plasma levels of testosterone, dihydrotestosterone and salivary testosterone levels were significantly lower in patients on haemodialysis than in controls. There was also a reduction in 5 alpha-reductase activity as evidenced by a reduced 5 alpha DHT/T ratio. SHBG levels were comparable to those found in eugonadal men. No differences were found in the parameters studied before and after 6 h haemodialysis. It is concluded that haemodialysis is not of obvious benefit to gonadal function.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1984

Somatostatin inhibits prolactin release from the lactotroph primed with oestrogen and cyproterone acetate in man.

The present study investigated the effect of administration of somatostatin (SRIF) on the release of prolactin in men. No effect was observed when SRIF was administered to eugonadal men. Release of prolactin was inhibited, however, when SRIF was administered to oestrogen-treated agonadal subjects (male-to-female trans-sexuals) and to an even greater degree when subjects had been pretreated with a combination of oestrogen and cyproterone acetate. This is consistent with findings in the rat. Thus in man, as in the rat, SRIF can inhibit prolactin secretion, but only after treatment with oestrogen.

Adult↗
PubMedDate not supplied

Basal and LHRH-stimulated gonadotropin levels and the circadian rhythm of testosterone and the effect of exogenous testosterone thereon.

In seven eugonadal men, aged 20-26 years, a fall in plasma and saliva testosterone (T) levels between 8.00 and 16.00 h of the day was observed, but plasma oestradiol-17 beta levels did not show a significant variation. These findings substantiate the existence of a circadian rhythm in T levels. Concurrent with the decrease of T levels over the day, a small but significant rise in basal LH, but not in LHRH-stimulated LH levels were observed. Then the fall of plasma and saliva T levels over the day was prevented by the administration of 80 mg testosterone undecanoate (Andriol, Organon) by mouth at 8.00 h. A rise in plasma T and even more in saliva T levels was measured, which persisted till at least 16.00 h. At this hour basal LH, but not LHRH-stimulated LH levels appeared to be slightly, though significantly depressed. From our data we conclude that fluctuations of T levels of the magnitude of 25% around the baseline values, affect slightly basal LH levels, but not LHRH-stimulated LH levels.

Adult↗
PubMedDate not supplied

Androgens in the feedback regulation of gonadotropin secretion in men: effects of administration of dihydrotestosterone to eugonadal and agonadal subjects and of spironolactone to eugonadal subjects.

To study the role of androgens in the feedback regulation of gonadotropin secretion, we measured the effects of administration of dihydrotestosterone undecanoate (DHTU) and of spironolactone. Basal and LRH stimulated LH/FSH levels were determined in: Six eugonadal men, before and after six weeks' DHTU 120 mg/day. Six agonadal subjects after 12 weeks' DHTU 120 mg/day. The results of B were compared to those of Six agonadal subjects without sex steroid treatment. Six eugonadal subjects were studied before and after six weeks' administration of spironolactone. In the two groups of eugonadal subjects, administration of either dihydrotestosterone or spironolactone had no effect on basal and LRH-stimulated gonadotropin levels. A clear but modest suppression was observed in agonadal subjects. Possibly DHT exerts some suppressive effect on gonadotropin secretion in the absence of other testicular products (estradiol, testosterone, inhibin), known to play a role in the negative feedback regulation. From these data it seems unlikely that in the eugonadal male circulating DHT has an important role in the feedback regulation of gonadotropin secretion.

Adult↗
PubMedDate not supplied

Interaction of inhibin and estrogens on basal and LRH-stimulated gonadotropin levels.

In order to study the action of estrogens and inhibin and their interaction with gonadotropin secretion in men, we measured basal and LRH-stimulated gonadotropin secretion before and after six weeks' administration of tamoxifen in two groups of men. A) Six men with impaired spermatogenesis with basal levels of FSH, LH, testosterone and estradiol within the range of reference values in our laboratory. B) Six men with severely impaired spermatogenesis. LH, testosterone and estradiol levels were within reference values, whereas FSH was at least 100% above the upper limit of reference values. Mean testosterone and estradiol levels were not different in either groups. Inhibin levels were presumed to be normal in group A and decreased in group B. Although within reference values, basal LH levels in group B were slightly but significantly higher than in group A. The response of LH to LRH in group B exceeded that of group A. This suggests that inhibin has a slightly inhibitory effect on basal LH and even more so on LRH-induced LH secretion. After tamoxifen administration basal FSH levels rose far more in group B than in group A. The LRH-induced LH release increased in both groups, the LRH-stimulated FSH release, however, increased only in group A. We conclude that estrogens and inhibin have a strongly synergistic negative feedback action on basal FSH secretion, and to a limited extent on basal LH secretion. In the presumed presence of inhibin (group A) the FSH additionally synthesized through the action of anti-estrogens, can be released by LRH administration, whereas FSH is probably spontaneously released in the presumed deficiency of inhibin (group B). With LH this phenomenon is less obvious.

Adult↗
PubMedDate not supplied

Estrogens in the feedback regulation of gonadotropin secretion in men: effects of administration of estrogen to agonadal subjects and the antiestrogen tamoxifen and the aromatase inhibitor delta'-testolactone to eugonadal subjects.

To elucidate the specific role of estrogens in the feedback regulation of gonadotropin secretion in men, basal and LRH-stimulated gonadotropin levels were studied in: Six agonadal subjects Six agonadal subjects continuously treated with 50 micrograms ethinylestradiol Six eugonadal subjects, treated with the aromatase inhibitor delta'-testolactone, which induced a reduction of estrogen levels, independently of testosterone. Further, to determine whether estrogens exert differential effects in time on LH and FSH secretion, the anti-estrogen tamoxifen was administered to: Six eugonadal subjects for two weeks and Six eugonadal subjects for six weeks. It was found that estrogens have a strong suppressive effect on both LH and FSH secretion. However, changes in estrogen levels and blocking of estrogen receptors are followed more rapidly by FSH than LH. Estrogens affect LRH-induced LH release more than basal LH levels; basal and LRH-stimulated FSH are approximately equally influenced. Basal and LRH-induced LH secretion are known to be more dependent upon previous LRH stimulation than FSH secretion. Since FSH followed changes of estrogens more rapidly than LH did, we postulate that the negative feedback action of estrogens on: LH secretion is predominantly exerted at the level of the hypothalamus, through inhibition of LRH secretion FSH secretion predominantly at the level of the pituitary through a direct action on the gonadotroph.

Adult↗
PubMedDate not supplied

A ten-year safety study of the oral androgen testosterone undecanoate.

Testosterone undecanoate (Andriol) is an oral androgen that provides the hypogonadal patient with the unmodified testosterone molecule. It was introduced in the mid-1970s. This is a report on the safety of this oral androgen. Of 35 men originally included in the study, 33 could be followed up for a minimum of 10 years. In them no alteration in the biochemical parameters of liver function could be detected. Upon annual measurements (7-9 hours after ingestion of testosterone undecanoate), serum levels of testosterone ranged between 5.4 +/- 1.9 and 6.5 +/- 1.9 nmol/L (normal range 8-24) and of 5 alpha-dihydrotestosterone between 3.2 +/- 1.8 and 3.5 +/- 1.7 nmol/L (normal range 0.8-2.5). These levels remained constant during the study period, indicating that there is no increased hepatic enzymatic breakdown of the androgen over time. Eight men were older than 50 years at the start of the study. Over the 10-year period in two of them a mild reduction in urine flow was measured, whereas in the other six this could not be demonstrated. Digital examination of the prostate did not reveal signs of prostate tumors. Testosterone undecanoate appears to be a safe oral androgen. A yearly checkup of the patient on therapy with this androgen seems adequate.

Administration, Oral↗