Imprinting of Male Sex Tissues by Neonatal Endogenous Androgens in Mice

Jean‐Faucher, Ch.; Berger, Michel; Gallon, Ch.; Turckheim, M. de; Veyssière, G.; Jean, C

doi:10.1159/000180537

Cited by 10 publications

(2 citation statements)

References 14 publications

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“…While exposure to T neonatally is essential for normal development of sex accessory organs [7], high neonatal T levels reduce weights and induce persistent biochemical defects in adult accessory organs of rats [8,9] and mice [10]. Similarly, anti-androgen exposure in neonatal male mice affects the functional development of accessory organs and fertility [11] as well as androgen responsiveness at adulthood [12]. Besides androgens, estrogens have also been reported to contribute significantly to the regulation of sex accessory organs [13].…”

Section: Introductionmentioning

confidence: 99%

Imprinting by Neonatal Sex Steroids on the Structure and Function of the Mature Mouse Prostate1

Singh

Handelsman

1999

Biology of Reproduction

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Perinatal sex-steroid exposure may result in permanent modifications in the structure and function of the prostate gland. The mechanism of such long-range alterations in hormonal sensitivity is not known. This study aimed to define the molecular requirements for neonatal sex-steroid imprinting and to investigate whether combined administration of neonatal androgens and estrogens had synergistic effects upon the mature mouse prostate. Since the interaction between endogenous and exogenous sex steroids in normal mice makes it difficult to dissociate direct from indirect effects, we used the hypogonadal (hpg) mouse, characterized by congenital androgen deficiency yet still fully responsive to exogenous androgens. Newborn mice (Days 1-2) were administered a single s.c. injection of androgens alone or in combination with an estrogen followed by testosterone-induced maximal prostate growth at maturity. The final effects were determined in 7-wk-old mice through study of ductal architecture in microdissected ventral prostates (VP) and quantitation of volume densities and diameters of prostate tissue components. A single neonatal dose of androgens, but not of estrogen, increased branching morphogenesis and VP weights at adulthood. These effects did not differ significantly between various androgens; in addition, combined androgen and estrogen treatment failed to demonstrate any synergistic effects on the prostate. We conclude that neonatal androgens induce long-range effects upon the mature VP structure as well as its secretory function and that this imprinting occurs via the androgen receptor without requiring aromatization of androgens. However, these conclusions, based on a specific treatment protocol, are confined only to the distal segment of VP, and effects of neonatal sex-steroid exposure in other regions or lobes of VP may differ.

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Section: Introductionmentioning

confidence: 99%

Imprinting by Neonatal Sex Steroids on the Structure and Function of the Mature Mouse Prostate1

Singh

Handelsman

1999

Biology of Reproduction

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“…It remains to be determined whether some degree of imprinting by the high concentrations of androgens in the first weeks after birth led to an increase in responsiveness to the lower levels of steroids in the subsequent weeks. An irreversible imprinting by neonatal androgens has been shown in male sex tissues of some laboratory rodents (12)(13)(14)(15)(16), and has been suggested as being responsible for the maintenance of secretion by the seminal vesicles in castrated hamsters (17). An extratesticular support seems to be ruled out in our study by the data from the castrate males.…”

Section: Journal Of Endocrinology (1997) 137mentioning

confidence: 51%

Effects of castration on early postnatal development of male accessory sex glands in the domestic pig

Raeside

Friendship²,

Vrablic³

1997

European Journal of Endocrinology

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In the neonatal pig there is a remarkable production of steroids by the testes for the first few weeks after birth. Several androgens and estrogens reach a peak at about one month of age. In order to gain an understanding of the significance of this early steroid secretion we examined the effect on accessory sex glands of removal of the testes before the peak in these compounds would have occurred. Pigs were castrated (n=38) at 2-3 weeks of age, with littermates serving as intact controls (n=33). Animals were killed at ages ranging from 4-12 weeks. Blood samples were taken and both bulbourethral (BU) and vesicular glands (VG) were removed, as well as the testes of intact males. Organ pairs were weighed and samples fixed for histological examination. Plasma samples were stored at ¹20 ЊC until assayed, without extraction, for testosterone, dehydroepiandrosterone sulfate (DHEAS) and estrone sulfate (E 1 S) by radioimmunoassay. Of the hormones measured, plasma DHEAS concentrations were highest, but variable over the time period (304.2 and 75.6 nmol/l; 87.7 and 21.8 ng/ml at 5 and 12 weeks respectively). E 1 S declined steadily from 76.6 to 5.8 nmol/l (20.7 to 1.56 ng/ml). Testosterone levels were lowest but rose from 2.67 to 9.54 nmol/l (0.77 to 2.75 ng/ml). No steroids were clearly detectable in samples from castrated males. Testes weights (wt) increased fourfold, as did body wt for both intact and castrate males. Both BU and VG showed absolute increases in wt (3.5× and 5× respectively) in intact males, and each was about 2.8× greater than in castrates (mg/kg body wt). Histological sections were markedly distinctive for both BU and VG between intact and castrate animals, and a lack of developmental changes in both glands was noted in the castrates. Our findings provide clear evidence of an influence of the testes on accessory sex glands in the early postnatal life of the pig.

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Experimental diabetes has adverse effects on the differentiation of ventral prostate during sexual maturation of rats

et al. 2005

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Diabetes mellitus of both type I (insulin-dependent) and type II (noninsulin-dependent) has adverse effects on male sexual and reproductive functions in adolescent boys and men, which include impairment of spermatogenesis, reduced sperm count, serum testosterone and seminal fluid volume, impotency, and loss of libido. Streptozotocin (STZ)-induced diabetes in rats provides a relevant model to study reproductive dysfunction under diabetic conditions, as they exhibit a number of deficits in reproductive function that resemble those seen in human diabetics. Therefore, the present investigation is aimed to understand the effects of STZ diabetes on the structure and development of ventral prostate during the critical period of sexual maturation in rats. Prepubertal (40-days-old) male Wistar rats were made diabetic by single injection of STZ (120 mg/kg body weight, intraperitoneally). Induction of diabetes was confirmed by serum insulin titer, hyperglycemia, and polyuria. To another set of STZ-diabetic rats, after 3 days of diabetes induction, insulin was replaced at a dose of 3 U/100 g body weight, subcutaneously in two equally divided doses at 8:00 AM and 6:00 PM. Diabetes caused regression of prostate, leading to a decrease in the absolute weight. Histologically, glandular epithelium has undergone shrinkage with transformation of acinar cells into low cuboidal type with less prominent secretory granules and blebs. Nevertheless, the secretory activity was not totally abolished. Interstitial space was increased due to shrinkage of glandular epithelium. Histomorphometric studies on the tubular diameter, volume and surface density of acinar epithelium, lumen, and stroma also support regressive changes in prostate. Insulin replacement prevented the detrimental effects of diabetes partially. These findings implicate the adverse effects of STZ diabetes on the differentiation of ventral prostate during sexual maturation.

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Imprinting of Male Sex Tissues by Neonatal Endogenous Androgens in Mice

Cited by 10 publications

References 14 publications

Imprinting by Neonatal Sex Steroids on the Structure and Function of the Mature Mouse Prostate1

Imprinting by Neonatal Sex Steroids on the Structure and Function of the Mature Mouse Prostate1

Effects of castration on early postnatal development of male accessory sex glands in the domestic pig

Experimental diabetes has adverse effects on the differentiation of ventral prostate during sexual maturation of rats

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