Effects Of 17α-methyltestosterone Research Articles

Effects of 17α-methyltestosterone and letrozole on growth and gonadal development in largemouth bass (Micropterus salmodies)

In order to optimize the parameters for reversing masculinization and establish the techniques for sex induction of pseudo-males and creation of all-female fry in largemouth bass (Micropterus salmodies, LMB), 15-day-old LMB (1.00 ± 0.10 cm in length, 0.10 ± 0.01 g in weight) were fed a diet supplemented with either 17α-methyltestosterone (MT) or letrozole (LE) and their combination. The experimental groups were M20 (20 mg/kg MT), L20 (20 mg/kg LE) and M10L10 (10 mg/kg MT and 10 mg/kg LE). The control group, named C, was not feed MT or LE. After 60 days, exogenous hormone in the diets was stopped and the effects of MT and LE on growth, male ratio, and gonadal development in LMB were evaluated. At 12-month-old, blood and gonadal tissue samples were collected to measure sex steroid hormones levels, analyze expression levels of dmrt1 and cyp19a1a genes, as well as examine the gonads morphology. The results showed no significant differences in growth between the experimental groups and the control group after a 60-day feeding period with the formulated diet (p > 0.05). The sex reversal ratio of M20, L20, M10L10 were 95.00%, 80.00%, 76.47%, respectively. The gonadal tissue sections showed that the gonadal structure of masculinized fish morphologic resembled that of control male fish. At 12-month-old, the sex reversal ratio in M20, L20, M10L10 and C groups were 100%, 86.67%, 73.33% and 50.00%, respectively. The testicular of pseudo-male fish in the M20 group exhibited well-developed morphology similarities to that of the control group males. However, the testes of pseudo-male fish in the L20 and M10L10 groups were smaller size Estradiol (E2) levels in the experimental groups was significantly lower than those in the control group females (p < 0.05), while testosterone (T) levels were significantly higher than that of the control group (p < 0.05). Compared to the female fish in the control group, pseudo-male fish from all experimental groups showed significantly upregulated expression of dmrt1 (p < 0.05), and significantly downregulated expression of cyp19a1a (p < 0.05). Pseudo-males selected from group M20 exhibited a significantly higher proportion of female offspring (92.00%) compared to the control group (46.50%). In summary, 20 mg/kg MT was the optimal inducing concentration.

Identification of Insulin-like Growth Factor (IGF) Family Genes in the Golden Pompano, Trachinotus ovatus: Molecular Cloning, Characterization and Gene Expression.

Insulin-like growth factors (IGFs) are hormones that primarily stimulate and regulate animal physiological processes. In this study, we cloned and identified the open reading frame (ORF) cDNA sequences of IGF family genes: the insulin-like growth factor 1 (IGF1), insulin-like growth factor 2 (IGF2), and insulin-like growth factor 3 (IGF3). We found that IGF1, IGF2, and IGF3 have a total length of 558, 648, and 585 base pairs (bp), which encoded a predicted protein with 185, 215, and 194 amino acids (aa), respectively. Multiple sequences and phylogenetic tree analysis showed that the mature golden pompano IGFs had been conserved and showed high similarities with other teleosts. The tissue distribution experiment showed that IGF1 and IGF2 mRNA levels were highly expressed in the liver of female and male fish. In contrast, IGF3 was highly expressed in the gonads and livers of male and female fish, suggesting a high influence on fish reproduction. The effect of fasting showed that IGF1 and mRNA expression had no significant difference in the liver but significantly decreased after long-term (7 days) fasting in the muscles and started to recover after refeeding. IGF2 mRNA expression showed no significant difference in the liver but had a significant difference in muscles for short-term (2 days) and long-term fasting, which started to recover after refeeding, suggesting muscles are more susceptible to both short-term and long-term fasting. In vitro incubation of 17β-estradiol (E2) was observed to decrease the IGF1 and IGF3 mRNA expression level in a dose- (0.1, 1, and 10 μM) and time- (3, 6, and 12 h) dependent manner. In addition, E2 had no effect on IGF2 mRNA expression levels in a time- and dose-dependent manner. The effect of 17α-methyltestosterone (MT) in vitro incubation was observed to significantly increase the IGF3 mRNA expression level in a time- and dose-dependent manner. MT had no effect on IGF2 mRNA but was observed to decrease the IGF1 mRNA expression in the liver. Taken together, these data indicate that E2 and MT may either increase or decrease IGF expression in fish; this study provides basic knowledge and understanding of the expression and regulation of IGF family genes in relation to the nutritional status, somatic growth, and reproductive endocrinology of golden pompano for aquaculture development.

Effects of 17α-Methyltestosterone on the Transcriptome and Sex Hormones in the Brain of Gobiocypris rarus

17α-Methyltestosterone (MT), a synthetic environmental endocrine disruptor with androgenic effects, has been shown to disrupt the reproductive system and inhibit germ cell maturation in Gobiocypris rarus. To further investigate the regulation of gonadal development by MT through the hypothalamic-pituitary-gonadal (HPG) axis, G. rarus were exposed to 0, 25, 50, and 100 ng/L of MT for 7, 14, and 21 days. We analyzed its biological indicators, gonadotropin-releasing hormone (GnRH), gonadotropins, reproduction-related gene expression, and brain tissue transcriptome profiles. We found a significant decrease in the gonadosomatic index (GSI) in G. rarus males exposed to MT for 21 days compared to the control group. GnRH, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels, as well as the expressions of the gnrh3, gnrhr1, gnrhr3, fshβ, and cyp19a1b genes, were significantly reduced in the brains of both male and female fish when exposed to 100 ng/L MT for 14 days compared to the controls. Therefore, we further constructed four RNA-seq libraries from 100 ng/L MT-treated groups of male and female fish, obtaining 2412 and 2509 DEGs in male and female brain tissue, respectively. Three common pathways were observed to be affected in both sexes after exposure to MT, namely, nicotinate and nicotinamide metabolism, focal adhesion, and cell adhesion molecules. Furthermore, we found that MT affected the PI3K/Akt/FoxO3a signaling pathway through the upregulation of foxo3 and ccnd2, and the downregulation of pik3c3 and ccnd1. Therefore, we hypothesize that MT interferes with the levels of gonadotropin-releasing hormone (GnRH, FSH, and LH) in G. rarus brains through the PI3K/Akt/FoxO3a signaling pathway, and affects the expression of key genes in the hormone production pathway (gnrh3, gnrhr1 and cyp19a1b) to interfere with the stability of the HPG axis, thus leading to abnormal gonadal development. This study provides a multidimensional perspective on the damaging effects of MT on fish and confirms that G. rarus is a suitable model animal for aquatic toxicology.

Effect of 17α-methyltestosterone (MT) on oxidation stress in the liver of juvenile GIFT tilapia, Oreochromis niloticus.

The normal dose of 17α-methyltestosterone (MT) used in fish farming was 60 mg/L, and now the analysis of residual androgens was carried out in waste water obtained from the Beijing area, which could be detected in levels ranging from 4.1 to 7.0 ng/L. For the purpose of aquatic early warning, the present study clearly demonstrated that chronic exposure by higher concentration of MT than environmental relevant concentrations could trigger oxidative stress response to juvenile tilapia by modulating hepatic antioxidant enzyme activities and gene transcription. Some antioxidative parameters (T-GSH, GSH/GSSG and MDA) were significant decreased under 0.5 mg/L MT exposure at 7 and 14 days. Some antioxidant enzymes (SOD, CAT and GST) and transcriptional changes (sod and cat) were revealed significant decreases for MT treated groups at 7 days. Total antioxidant capacity was significant increased only in 5 mg/L MT exposure groups, but GR activities were not affected all through the whole exposure period. Almost all of the antioxidant enzymatic genes detected in the present study were showed significant increments for MT exposure both at 14 and 21 days, and the genotoxicity profile of antioxidant enzymatic genes were revealed dose-dependent manner. This study presented evidence that MT could result in oxidative stress response in the early stages of GIFT tilapia.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-1946-6) contains supplementary material, which is available to authorized users.

Molecular cloning, characterization, and expression profiles of androgen receptors in spotted scat (Scatophagus argus).

Androgen plays critical roles in vertebrate reproductive systems via androgen receptors (ARs). In the present study, the full-length spotted scat (Scatophagus argus) androgen receptor (sAR) cDNA sequence was cloned from testis. The sAR cDNA measured 2448 bp in length with an open-reading frame of 2289 bp, encoding 763 amino acids. Amino acid alignment analyses showed that the sARs exhibited highly evolutionary conserved functional domains. Phylogenetically, the sARs clustered within the ARβ common vertebrate group. Real-time polymerase chain reaction (RT-PCR) revealed that sAR expression varied in level and distribution throughout the tissues of both females and males. sAR expression was detected during testicular development by quantitative RT-PCR. The results showed that the highest transcription of sARs was observed in the mid-testicular stage, and remained at a high expression level until the late-testicular stage. In addition, the effects of 17α-methyltestosterone (MT) and estrogen (E2) on the expression of sARs in ovaries were determined using quantitative RT-PCR. sAR expression increased at 12 and 24 h post-MT treatment and decreased with E2 treatment. The present study provides preliminary evidence indicating gonadal plasticity of spotted scat under exogenous steroidal hormone treatments. It also provides a theoretical basis for sex reversal and production of artificial pseudo-males for female monosex breeding.

Effects of 17α-methyltestosterone on the reproduction of the freshwater snail Biomphalaria glabrata

17-α-methyltestosterone (MT) is a synthetic hormone used in fish hatcheries to induce male monosex. Snails hold promise as possible test models to assess chemicals acting on the endocrine system. Biomphalaria glabrata is an aquatic gastropod mollusk (Pulmonata, Planorbidae) that can be easily maintained in aquaria, predisposing the species for use in ecotoxicological testing. This study evaluated the reproductive effects of MT on B. glabrata by examining histological changes and its reproductive performance. Ten snails per group were exposed for 4 weeks to different concentrations of MT (0.01, 0.1, and 1.0 mg/L). The total number of laid eggs, egg mass per group, size of type V oocytes, and production of spermatozoids were determined. Reproduction of B. glabrata was affected by MT. At the lowest concentration (0.01 mg/L), MT caused a statistically significant increase in the number of egg mass per snail compared with controls unexposed to MT. Histopathology analyses showed an increase in the sperm production at the higher MT concentrations of 0.1 and 1.0 mg/L. Chromatographic analyses of water samples showed that MT concentrations rapidly declined within a 96-h period. These results highlight the importance of giving more support to regulatory authorities, since MT is not registered for use on fish hatcheries in many countries around the world. Wastewater from fish farms discharged into aquatic ecosystems should be monitored for MT residues, since its presence could compromise the reproduction of other native snail species.

Enhancing spawning in the grey mullet ( Mugil cephalus) by removal of dopaminergic inhibition

A dot-blot immunoassay for the detection of vitellogenin (Vtg) in plasma of adult grey mullet ( Mugil cephalus) was developed. The assay identified the sex of the tested fish prior to detectable gonadal development, enabling the establishment of broodstock at the desired ratio of 7:4 females to males. This broodstock was maintained under natural photoperiod, and used to study the relative effect of gonadotropin-releasing hormone (GnRH) and dopamine antagonists on oocyte maturation and ovulation, as well as the effect of 17α-methyltestosterone (MT) on spermiation. Three groups of females were treated with: (i) a single injection of dopamine antagonist, domperidone (Dom), (ii) GnRH analog (GnRHa) administered via ethylene-vinyl acetate copolymer (EVAc) slow-release implants or (iii) a combination of both Dom and GnRHa. Males were treated with MT, administered via EVAc slow-release implants. An additional group of untreated fish was used as a control. The Dom treatment proved to be more potent than the GnRHa treatment, and did not differ significantly from the combined treatment. The Dom and Dom + GnRHa treatments accelerated oocyte development and increased plasma estradiol levels equally, whereas the GnRHa treatment did not vary significantly from the control. MT was found to be a potent spermiating agent, which enhanced steady milt production in all treated males. In contrast, no spontaneous spermiation occurred in untreated males. Plasma 11-ketotestosterone (11-KT) levels were significantly higher in MT-treated males than in the controls. Interestingly, MT-treated males held with the GnRHa + Dom-treated females showed higher levels of plasma 11-KT than those held with GnRHa-treated females, indicating an additive effect which is probably attributable to female pheromones. Fully mature females were induced to spawn by injecting GnRHa alone or coupled with metaclopramide (a dopamine D2 receptors antagonist). The combined treatment, which included a dopamine antagonist, was found to be more potent in inducing ovulation and spawning as compared to GnRHa alone. In conclusion, our data suggest that dopaminergic inhibition is a major barrier along the reproductive axis that arrests spontaneous spawning in captive mullets.

Effects of 17α-methyltestosterone on uterine morphology and heat shock protein expression are mediated through estrogen and androgen receptors

Testosterone and the synthetic androgen, 17α-methyltestosterone (MT), have been shown to increase uterine weights and alter uterine morphology. However, whereas the mechanism of action of testosterone in the uterus has been studied, it is not known if the actions of MT are mediated through androgen (AR) or estrogen (ER) receptors. In the present study, we have shown that MT, at 0.5 or 10 mg/kg per day, increases uterine weight and alters uterine morphology in a dose-dependent manner. Co-administration of the anti-androgen, flutamide, or the anti-estrogen, ICI 182,780, with MT revealed that the effects of the low dose of MT are mediated through the ER, whereas those of the high dose are mediated through both the ER and AR. In addition, we have studied the effects of MT on uterine heat shock proteins (hsps), a group of estrogen-regulated proteins whose levels increase in response to growth signals and protein damage. MT increased levels of hsp90α, hsp72, and grp94. All effects on uterine hsp levels were antagonized by the anti-estrogen and not the anti-androgen. Collectively, the results of the present study indicate that the effects of MT in the uterus are mediated through the AR and ER.

Activation of the growth hormone/insulin-like growth factor axis by treatment with 17α-methyltestosterone and seawater rearing in the tilapia, Oreochromis mossambicus

Effects of 17α-methyltestosterone (MT) treatment and environmental salinity on the growth hormone (GH)/insulin-like growth factor (IGF) axis were examined in the euryhaline tilapia, Oreochromis mossambicus. Yolk-sac fry were collected from brood stock in fresh water (FW). After yolk-sac absorption, they were assigned randomly to 1 of 4 groups: FW, MT treatment in FW, SW, and MT treatment in seawater (SW). After 147 days, FW controls had the lowest levels of GH mRNA followed by FW fish treated with MT and SW control fish. Seawater fish fed with a diet containing MT, which grew the fastest, had significantly higher levels of GH mRNA than all the other groups. A significant correlation was observed between GH mRNA and the size of the individual fish. By contrast, plasma GH levels did not vary significantly among the groups. Pituitary GH mRNA levels, plasma IGF-I levels, and fish size varied in a correlated pattern, i.e., SW+ MT> FW+ MT= SW control > FW control. The tilapia pituitary produces two prolactins (PRLs), PRL 177 and PRL 188. Prolactin 177, but not PRL 188, exhibits growth-promoting actions in FW tilapia. Pituitary mRNA levels of both PRLs were significantly higher in fish reared in FW than those reared in SW. Treatment with MT significantly increased mRNA levels of both PRLs in FW, but had no effect on SW fish. No correlation was seen between plasma PRL levels and growth or between PRL mRNA levels and growth. These results indicate that SW rearing and MT treatment stimulate the GH/IGF-I axis, and suggest that pituitary GH mRNA at this stage of development is a better indicator of growth than plasma levels of GH and IGF-I.

Sex reversal in black crappie Pomoxis nigromaculatus: effect of oral administration of 17α-methyltestosterone on two age classes

The masculinizing effect of 17α-methyltestosterone (MT) on two age classes of black crappie Pomoxis nigromaculatus was investigated. Broodstock were induced to spawn by intramuscular injection of human chorionic gonadotropin hormone (hCG). Fry produced were divided into two age classes, age I (40 days old), and age II (60 days old). Age I fry were fed to satiety with feed containing MT at a concentration of 0, 30, or 60 mg/kg feed. Age II fry were fed MT at 60 mg/kg feed only. Both age classes were fed hormone treated diet for 30 days. Mean initial weight and length of age I fry were 0.21 ± 0.15 g and 23 ± 2.2 mm, respectively (mean ± SD), whereas age II fry were 0.22 ± 0.10 g and 24 ± 3.4 mm, respectively. Age I fry fed with 60 mg MT/kg feed yielded the highest (90%) mean percent males relative to all treatments (P < 0.01). Age I fry fed with 30 mg MT/kg feed produced 71% mean percent males that was significantly higher (P < 0.05) than age II fry fed with 60 mg MT/kg feed, and fry fed with control diet (P < 0.01). There was no significant difference in percent males between age II fry (58%) and control (51%). Two patterns of ovotestis were identified by histological examination. One pattern was dominated by ovarian tissue or Ovotestis-Mainly Testicular (OTMO), the other was dominated by testicular tissue or Ovotestis-Mainly Testicular (OTMT). Sex reversal in black crappie seems to be influenced by age more than size. This study reports the first successful masculinization of this species by hormonal treatment.

The Effects of 17α-Methyltestosterone, Methandrostenolone, and Nandrolone Decanoate on the Rat Estrous Cycle

Blasberg, M. E., C. J. Langan and A. S. Clark. The effects of 17α-methyltestosterone, methandrostenolone, and nandrolone decanoate on the rat estrous cycle. Physiol Behav 61(2) 265–272, 1997.—In a series of four separate experiments, the effects of anabolic-androgenic steroid (AAS) compounds on the estrous cycle of adult Long-Evans rats were examined. Sexual receptivity, vaginal cytology, and body weight were monitored throughout a 2-week baseline, AAS treatment, and recovery periods. In Experiments 1–3, subjects were administered 17α-methyltestosterone, methandrostenolone, or nandrolone decanoate at doses selected to mimic the human abuse levels of each compound. In these studies, the highest doses of 17α-methyltestosterone (7.5 mg/kg) and nandrolone decanoate (5.6 mg/kg) disrupted behavioral and vaginal cyclicity, whereas the highest dose of methandrostenolone (3.75 mg/kg) appeared to have slightly less robust effects. To compare effects on estrous cyclicity across AAS compounds, subjects in Experiment 4 received a single high dose (7.5 mg/kg) of each compound for 2 weeks. At this dose, all AAS compounds interfered with vaginal cyclicity, although effects on behavioral cyclicity and uterine weight were not uniform. Across all 4 experiments, AAS effects on body weight were minimal. The short-term administration of AAS compounds at levels commonly used by humans disrupts female neuroendocrine function in a dose-dependent manner.

The maturation of the salmon GnRH system and its regulation by gonadal steroids in masu salmon

Pituitary gonadotropin (GTH) secreting cells and brain gonadotropin-releasing hormone (GnRH) secreting neurons are known to be subjected to feedback control by gonadal steroid in teleosts. In masu salmon, Oncorhynchus masou, salmon GnRH (sGnRH) neurons in the ventral telencephalon (VT) and the preoptic area (POA) are involved in the control of GTH cells because sGnRH synthesis in these areas is activated with gonadal maturation. In this study, we attempted to clarify mechanisms of feedback control of sGnRH neurons by gonadal steroids. We examined the effects of 17α-methyltestosterone (MT) on sGnRH synthesis in yearling and 2-year-old female fish (which were immature during experimentation in May), and the effects of castration on sGnRH synthesis in underyearling precocious male fish in August. sGnRH synthesis in the POA, but not in the VT, was increased by MT administration in 2-year-old females only, indicating higher sensitivity to MT in the preoptic sGnRH neurons. Castration increased sGnRH synthesis in the VT but not in the POA. These results suggest that sGnRH neurons in the VT and those in the POA are differentially regulated by gonadal steroids.

Effects of 17α-methyltestosterone and 11β-hydroxyandrostenedione on gonad differentiation in the African catfish, Clarias gariepinus

Gonad development in Clarias gariepinus was studied from day 12 to day 114 after hatching. Ovaries were histologically recognizable at day 28 and characterized by the formation of an ovarian cavity and the presence of germ cells with nuclei in meiotic prophase. Testes were manifest at day 42 by their crenated appearance and the presence of spermatogonia and Leydig cells distributed between the germ cells. Exogenous androgens clearly affected the process of gonad differentiation. Treatment with 17α-methyltestosterone (30 μg/l) and 11β-hydroxyandrostenedione (300 μg/l) for 4 weeks from day 28 influenced the sex ratio in favour of males, and had no effect on the gonadosomatic index (GSI). In females, GSIs decreased when high dosages of methyltestosterone were administered. Methyltestosterone (100 μg/l) from day 14 had a feminizing effect. It is concluded that this effect is pharmacological rather than physiological.

Effect of 17α-methyltestosterone on the skin and gonads of freshwater male silver eels

Male silver eels kept in fresh water (FW) were injected with 17α-methyltestosterone (MT). They received 5, 10, 15, or 20 injections (8 μg/g every other day) or 6 or 9 injections (4 or 2.5 μg/g once a week) and were killed 24 hr after the last injection. Compared to solvent-injected controls, the treated eels appeared darker, the eye diameter was enlarged, the head and the pectoral and caudal fins were black and the melanophore index was maximal. The thickness of the skin (epidermis plus dermis) was significantly increased. Macroscopically, the organs of Syrski (juvenile testes) were slightly larger and less translucent, but the maximal gonosomatic index reached only 1–1.2 in two fishes. Stimulation started in the anterior part of the gonad. Microscopically, all stages of spermatogenesis and spermiogenesis were observed. After 20 injections (high dose, 40 days) or 6 (one case only) and 9 injections (low dose, 57 days), spermatids and spermatozoa were present. These positive results are compared to the negative data previously reported in other countries. The mode of action of the androgen is discussed. It is suggested that it acts for the most part directly on the gonad, but a participation of the pituitary cannot be ruled out, although gonadotrophs appeared only slightly stimulated.

The effect of 17α-methyltestosterone on the sex of the common carp,Cyprinus carpio (L.)

Dip treatment of fertilized eggs ofCyprinus carpio (L.) in 17α-methyltestosterone, followed by dietary administration of the same to the hatchlings over 50 days resulted in 54% males, 13% females and 33% sterile fish, while in the control group both sexes were in nearly equal numbers. The androgen-treated fish also showed better growth.

Effect of 17 alpha-methyltestosterone, estradiol-17 beta and synthetic LHRH on production of gonadotropic hormone in pituitaries of rainbow trout (organ culture).

Pituitary glands from 6-month-old sexually immature female rainbow trout, Salmo gairdneri, were kept in organ culture for 48 or 72 h. Certain groups of pituitaries were cultivated for 48 h on either control medium or medium with 17 alpha-methyltestosterone (MT), or with estradiol-17 beta (E2) in concentrations of 8.5 X 10(-7) M. Other groups of pituitaries were cultivated for 72 h on control medium, or for 48 h on either control medium or MT-medium or E2-medium, and subsequently for 24 h on medium with synthetic LHRH in concentrations of 8.5 X 10(-7) M and 8.5 X 10(-10) M. Gonadotropic (GTH) cells are identified by Alcian Blue-Periodic Acid Schiff-Orange G staining and the double-antibody immunoenzyme-cytochemical technique using anti-carp beta GTH as the first antibody. A quantitative histological procedure was used to study the nuclear size of the GTH cells in response to the different hormones. Secretory activity was estimated by measuring the gonadotropin (GTH) content in extracts of pituitaries, plasma, and the culture media every 24 h by radioimmunoassay. Cultivation on MT- or E2-enriched medium results in an increase of the total amount of GTH in the pituitary and medium, an accumulation of GTH in GTH-cells (approximately 20 percentage points) and an increase in their nuclear size, indicating a stimulation of GTH synthesis. However, autonomous GTH-release is not affected by these steroids. Subsequent cultivation of the pituitaries for 24 h with LHRH causes stimulation of GTH synthesis (approximately 20 percentage points). Preincubation with steroids increases the GTH synthesis capacity of LHRH only when used in a concentration of 8.5 X 10(-10) M. Moreover, 8.5 X 10(-7) M LHRH causes a stimulation of GTH-release. Preincubation of the pituitaries with steroids increases the responsiveness of GTH-cells to LHRH. It is concluded that GTH-production in pituitaries of immature female rainbow trout can be directly influenced by gonadal steroids and by a hypophysiotropic substance.

Effects of 17 alpha-methyltestosterone on the dorsal pad and tubercles of fathead minnows (Pimephales promelas).

The formation of breeding tubercles and a mucus-secreting dorsal pad in male and female fathead minnows is induced by 17α-methyltestosterone. Neither lactotrophic hormone (LTH) nor human chorionic gonadotropin induced dorsal pad or tubercle formation in the dosages used. LTH (with androgen) may delay loss of mucus cells at the end of the breeding season.

Histological Effects of 11-Ketotestosterone, 17α-Methyltestosterone, Estradiol, Estradiol Cypionate, and Cortisol on the Interrenal Tissue, Thyroid Gland, and Pituitary Gland of Gonadectomized Sockeye Salmon (Oncorhynchus nerka)

Effects of two androgens, two estrogens, and cortisol in gonadectomized sockeye salmon (Oncorhynchus nerka) were investigated. Males were injected with 11-ketotestosterone, 17α-methyltestosterone, or cortisol for 4 or 7 weeks. Females were injected with estradiol, estradiol cypionate, or cortisol for 8 weeks.Both the androgens and the estrogens caused interrenal hypertrophy. The effect of 17α-methyltestosterone was stronger than that of 11-ketotestosterone, and of the two estrogens used, estradiol cypionate exerted the most marked effect. Cortisol brought about a slight atrophy of the interrenal tissue.A pronounced histological activation of the small thyroid follicles was induced by the two androgens. The estrogens exerted no visible effect on the thyroid gland, and cortisol treatment caused a slight reduction in the height of the follicular epithelium.In the gonadectomized control fish of both sexes, gonadotrophs were small and practically all devoid of granules. All four sex steroids induced the appearance of many granulated PAS-positive gonadotrophs, particularly in the anterior part of the proximal pars distalis. This effect is considered on activation of the gonadotrophs. Cortisol administration induced pronounced degranulation and atrophy of the corticotrophs and this effect was strongest in the males. Neither the androgens nor the estrogens visibly affected the corticotrophs.

Effect of 17-alpha-methyltestosterone on steroid formation by rat adrenal tissue.

The addition of 17α-methyltestosterone to rat adrenals suppressed the conversion of 4-14C-labeled progesterone and 11-deoxycorticosterone to the corticosteroids, including corticosterone, 18-hydroxy-11-deoxycorticosterone, aldosterone, and more polar substances, such as 18-hydroxycorticosterone. The inhibition depended upon the dose of 17α-methyltestosterone; the formation of substances with the polarity of aldosterone or greater were most sensitive. The 17α-methyltestosterone appears to act as a competitive substrate for the adrenal hydroxylating enzymes because it is itself metabolized to more polar products. The main product, 11β-hydroxy-17α-methyltestosterone, did not appear to inhibit hydroxylation significantly.