Regulation of the pituitary 5α-reductase activity by gonadotropin releasing hormone and testosterone in the adult male rat

Vanderstichele, Hugo; Eechaute, W.; Lacroix, E

doi:10.1016/0022-4731(90)90201-3

Cited by 5 publications

(2 citation statements)

References 29 publications

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“…In fact, in the presence of GnRHa, testosterone caused a niarked increase in blood levels of FSH. A coniparable androgen-induced increase in FSH in rats treated with G n R H agonists or antagonists has been observed by several other investigators but the mechanism underlying this phenomenon remains poorly understood (Rhea et a!., 1986;Bhasin et d., 1987;Vanderstichele et al, 1990;Behre et al, 1992). An attempt was made to provoke a more selective increase of testosterone within the testis by the use of a low dose of hCG.…”

Section: Discussionmentioning

confidence: 97%

Effect of androgens on the germ cell‐depleted testes of prenatally irradiated rats

et al. 1995

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To study the effect of androgens on somatic testicular cells, rats were rendered germ cell depleted by prenatal irradiation (RX). Adult RX rats were treated with a desensitizing dose of a GnRH agonist (GnRHa; Zoladex), combined with an antiandrogen (Nilutamide) to preclude all androgen effects, or combined with testosterone or hCG to restore androgen action. The effect of these treatments for 3 weeks on the weight of testes and accessory sex glands, hormones (LH, FSH, testosterone, inhibin), testicular proteins, the pattern of incorporation of [35S]-methionine into testicular proteins (studied by two dimensional gel electrophoresis) and steady state mRNA levels for transferrin and androgen-binding protein (ABP) were evaluated. Combined treatment with GnRHa and antiandrogen virtually eliminated gonadotrophins, androgens and androgen effects. Testicular weight was reduced to 50% of that observed in RX controls. Treatment with GnRHa and testosterone resulted in supraphysiological levels of testosterone and testicular weights comparable to those observed in RX controls. FSH levels in these animals, however, were in the normal range. A low dose of hCG also restored testicular weight in the presence of low concentrations of serum testosterone and low normal levels of FSH. Neither polyacrylamide gel electrophoresis of total testicular proteins nor two dimensional gel electrophoresis of [35S]-methionine labelled proteins revealed striking changes in distinct testicular proteins as a result of androgen withdrawal or androgen treatment. Dot blot hybridization showed a three-fold increase in the mRNA level for ABP (expressed per microgram total RNA) in the Sertoli cell enriched testes of RX rats. This level was barely influenced by androgen withdrawal or androgen administration. The mRNA level for transferrin was increased six-fold in RX rats. A 50% reduction of this level was observed after combined treatment with GnRHa and antiandrogen. It is concluded that, in the germ cell-depleted testis, the major effect of androgens is an overall increase in protein and RNA synthesis rather than a very important and selective increase of a few gene products.

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Section: Discussionmentioning

confidence: 97%

Effect of androgens on the germ cell‐depleted testes of prenatally irradiated rats

et al. 1995

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“…In contrast, others observed no change or increase in AR concentration and AR messenger RNA following castration (Schanbacher et al, 1984;Burgess and Handa, 1993;Choate and Resko, 1996). An increase in the 5␣-reductase activity in the pituitary after castration and subsequent decrease by androgen administration have been reported (Denef et al, 1974;Vanderstichele et al, 1990). Because 5␣-reductase is involved in the increased potency of T on prostate growth, a similar role of 5␣reductase could be expected in the pituitary.…”

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confidence: 99%

The Antigonadotropic Action of Testosterone but not 7α‐Methyl‐19‐Nortestosterone Is Attenuated Through the 5α‐Reductase Pathway in the Castrated Male Rat Pituitary Gland

BANDIVDEKAR,

KARP,

SUNDARAM

et al. 2000

Journal of Andrology

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The enzyme 5α‐reductase plays a significant role in the prostate to amplify the action of testosterone (T) by converting it to a more potent androgen, dihydrotestosterone (DHT). The role of 5α‐reductase in the testosterone feedback inhibition of gonadotropin secretion from the pituitary has not been elucidated. Therefore, we investigated the role of 5α‐reductase on T action in in vitro and in vivo models. Castration has been reported to increase the 5α‐reductase activity in pituitary glands. Hence, the effect of castration duration on the conversion of T to DHT by pituitary homoge‐nates and the responsiveness of pituitary monolayer cell cultures to gonadotropin‐releasing hormone (GnRH) challenge exposure were investigated. Incubation of [3H]‐T with pituitary homogenatesshowed that the conversion of T to 5α‐reduced metabolites was two‐to threefold greater in pituitaries from rats who had been castrated for 14 days compared with those castrated for 1 day. In addition, the GnRH‐stimulated release of LH from monolayer cell cultures of pituitaries from rats castrated for 1 day was twofold greater, whereas that from rats castrated for 2 weeks was six‐ to sevenfold greater compared with basal luteinizing hormone (LH) release. Hence we used rats castrated for 2 weeks to elucidate the role of 5α‐reductase in T feedback inhibition. The inhibitory effects of the androgens T, 19‐nortestosterone (19‐NT), and 7α‐methyl‐19‐nortestosterone (MENT) at 3 different concentrations (10−9, 10−7, and 10‐5 mol/L) on GnRH‐stimulated LH release from monolayer cell cultures of pituitaries from rats castrated for 2 weeks were examined. All 3 androgens showed dose‐dependent inhibition of LH release. MENT showed the greatest inhibition, followed by 19‐NT and T. In the presence of finasteride (a 5α‐reductase inhibitor), the inhibition of LH released by T and 19‐NT were significantly greater. The inhibitory effect of MENT, which does not undergo 5α‐reduction, was not altered by finasteride. In an in vivo study, rats castrated for 2 weeks received T with or without finasteride. There was a significantly greater suppression of serum LH in rats receiving T plus finasteride compared with those receiving T alone. These results suggested that 5α‐reductase in the pituitary is not obligatory for the inhibitory action of T on gonadotropin secretion in the castrated rat. The action of MENT, a nonreducible androgen, on the pituitary is not affected by 5α‐reductase.

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Opposite effects of dihydrotestosterone and estradiol on apoptosis in the anterior pituitary gland from male rats

et al. 2015

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Hormones locally synthesized in the anterior pituitary gland are involved in regulation of pituitary cell renewal. In the pituitary, testosterone (T) may exert its actions per se or by conversion to dihydrotestosterone (DHT) or 17β-estradiol (E2) by 5α-reductase and aromatase activity, which are expressed in this gland. Previous reports from our laboratory showed that estrogens modulate apoptosis of lactotropes and somatotropes from female rats. Now, we examined the in vitro and in vivo effects of gonadal steroids on apoptosis of anterior pituitary cells from adult male rats. T in vitro did not modify apoptosis in anterior pituitary cells from gonadectomized (GNX) male rats. DHT, a non-aromatizable androgen, exerted direct antiapoptotic action on total anterior pituitary cells and folliculo-stellate cells, but not on lactotropes, somatotropes, or gonadotropes. On the contrary, E2 exerted a rapid apoptotic effect on total cells as well as on lactotropes and somatotropes. Incubation of anterior pituitary cells with T in presence of Finasteride, an inhibitor of 5α-reductase, increased the percentage of TUNEL-positive cells. In vivo administration of DHT to GNX rats reduced apoptosis in the anterior pituitary whereas E2 exerted proapoptotic action and reduced cells in G2/M-phase of the cell cycle. In summary, our results indicate that DHT and E2 have opposite effects on apoptosis in the anterior pituitary gland suggesting that local metabolization of T to these steroids could be involved in pituitary cell turnover in males. Changes in expression and/or activity of 5α-reductase and aromatase may play a role in the development of anterior pituitary tumors.

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Regulation of the pituitary 5α-reductase activity by gonadotropin releasing hormone and testosterone in the adult male rat

Cited by 5 publications

References 29 publications

Effect of androgens on the germ cell‐depleted testes of prenatally irradiated rats

Effect of androgens on the germ cell‐depleted testes of prenatally irradiated rats

The Antigonadotropic Action of Testosterone but not 7α‐Methyl‐19‐Nortestosterone Is Attenuated Through the 5α‐Reductase Pathway in the Castrated Male Rat Pituitary Gland

Opposite effects of dihydrotestosterone and estradiol on apoptosis in the anterior pituitary gland from male rats

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