Somatostatin and dopamine receptor expression in lung carcinoma cells and effects of chimeric somatostatin-dopamine molecules on cell proliferation

To study somatostatin/dopamine (SS/D) synergy in a human cell system constitutively expressing SS and D receptors (SSR and DR, respectively), we characterized the expression of SSR and DR subtypes in the non-small-cell lung cancer line Calu-6, and then we evaluated the effect on cell proliferation of SS/D chimeric molecules (BIM-23A387 and BIM-23A370), which bind with high affinity both sst2 and D2R, and compared the results with those obtained by using SS-14 and subtype-selective SS analogs (SSA) and D agonists (DA). Because Calu-6 cells produce insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) peptides, which play a role in the autocrine/paracrine control of cell growth, we also investigated the effects of chimeric compounds on secretion and expression of IGF system components. Relative high levels of sst2 and the long isoform of the D2R were detected by real-time RT-PCR and Western blot in Calu-6, together with sst5 and to a lesser extent sst3 and D4R. BIM-23A387 and BIM-23A370 significantly inhibited growth of Calu-6, whereas IGF-IGFBP secretion or expression was unaffected, suggesting a direct inhibitory effect. The inhibition of cell growth, measured by both [3H]thymidine incorporation and cell count, was significantly lower when individual SSA and DA control peptides or subtype-specific SSA and DA were tested. BIM-23A370 was more potent than BIM-23A387 ( P < 0.001). These findings show that SS/D chimeras can inhibit Calu-6 proliferation in an IGF-independent manner and suggest that this enhanced potency might be because of the induction of SSR/DR dimerization. The Calu-6 cell line, constitutively expressing SSR and DR, provides a suitable model to elucidate the mechanism of action of SSA and DA on regulation of cell growth and to characterize the interaction between SSR and DR.

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The Inhibitory Effect of Sulforaphane on Bladder Cancer Cell Depends on GSH Depletion-Induced by Nrf2 Translocation

Molecules ◽

10.3390/molecules26164919 ◽

2021 ◽

Vol 26 (16) ◽

pp. 4919

Author(s):

Canxia He ◽

Luigina P. Buongiorno ◽

Wei Wang ◽

Jonathan C. Y. Tang ◽

Natalizia Miceli ◽

...

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cell Growth ◽

Cancer Cell ◽

Inhibitory Effect ◽

Bladder Cancer Cell ◽

High Dose ◽

Cell Growth And Migration ◽

T24 Cells ◽

And Migration

Sulforaphane (SFN), an isothiocyanate (ITCs) derived from glucosinolate that is found in cruciferous vegetables, has been reported to exert a promising anticancer effect in a substantial amount of scientific research. However, epidemical studies showed inconsistencies between cruciferous vegetable intake and bladder cancer risk. In this study, human bladder cancer T24 cells were used as in vitro model for revealing the inhibitory effect and its potential mechanism of SFN on cell growth. Here, a low dose of SFN (2.5 µM) was shown to promote cell proliferation (5.18–11.84%) and migration in T24 cells, whilst high doses of SFN (>10 µM) inhibited cell growth significantly. The induction effect of SFN on nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression at both low (2.5 µM) and high dose (10 µM) was characterized by a bell-shaped curve. Nrf2 and glutathione (GSH) might be the underlying mechanism in the effect of SFN on T24 cell growth since Nrf2 siRNA and GSH-depleting agent L-Buthionine-sulfoximine abolished the effect of SFN on cell proliferation. In summary, the inhibitory effect of SFN on bladder cancer cell growth and migration is highly dependent on Nrf2-mediated GSH depletion and following production. These findings suggested that a higher dose of SFN is required for the prevention and treatment of bladder cancer.

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Effects of novel somatostatin-dopamine chimeric drugs in 2D and 3D cell culture models of neuroendocrine tumors

Endocrine Related Cancer ◽

10.1530/erc-19-0086 ◽

2019 ◽

Vol 26 (6) ◽

pp. 585-599 ◽

Cited By ~ 2

Author(s):

Aura D Herrera-Martínez ◽

Rosanna van den Dungen ◽

Fadime Dogan-Oruc ◽

Peter M van Koetsveld ◽

Michael D Culler ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Growth ◽

Dopamine Receptor ◽

Neuroendocrine Tumors ◽

3D Model ◽

Serotonin Release ◽

Receptor Expression ◽

3D Cultures ◽

2D And 3D ◽

3D Spheroids

Control of symptoms related to hormonal hypersecretion by functioning neuroendocrine tumors (NETs) is challenging. New therapeutic options are required. Since novel in vitro tumor models seem to better mimic the tumor in vivo conditions, we aimed to study the effect of somatostatin and dopamine receptor agonists (octreotide and cabergoline, respectively) and novel somatostatin-dopamine chimeric multi-receptor drugs (BIM-065, BIM-23A760) using 2D (monolayer) and 3D (spheroids) cultures. Dose–response studies in 2D and 3D human pancreatic NET cell cultures (BON-1 and QGP-1) were performed under serum-containing and serum-deprived conditions. Cell proliferation, somatostatin and dopamine receptor expression (SSTs and D2R), apoptosis, lactate dehydrogenase, as well as serotonin and chromogranin A (CgA) release were assessed. The following results were obtained. 3D cultures of BON-1/QGP-1 allowed better cell survival than 2D cultures in serum-deprived conditions. SSTs and D2R mRNA levels were higher in the 3D model vs 2D model. Octreotide/cabergoline/BIM-065/BIM-23A760 treatment did not affect cell growth or spheroid size. In BON-1 2D-cultures, only BIM-23A760 significantly inhibited CgA release –this effect being more pronounced in 3D cultures. In BON-1 2D cultures, cabergoline/BIM-065/BIM-23A760 treatment decreased serotonin release (maximal effect up to 40%), being this effect again more potent in 3D cultures (up to 67% inhibition; with BIM-23A760 having the most potent effects). In QGP-1, cabergoline/BIM-065 treatment decreased serotonin release only in the 3D model. In conclusion, cultures of NET 3D spheroids represent a promising method for evaluating cell proliferation and secretion in NET cell-line models. Compared to 2D models, 3D models grow relatively serum independent. In 3D model, SST-D2R multi-receptor targeting drugs inhibit CgA and serotonin secretion, but not NET cell growth.

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Signaling Mechanisms of Anti-Proliferation by Sphingosine 1-Phoshate(S1P) on Acute Promyelocytic Leukemia(APL) Cell Lines.

Blood ◽

10.1182/blood.v104.11.4468.4468 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4468-4468

Author(s):

Yeung-Chul Mun ◽

Eui-Soo Hwang ◽

Kyoung-Eun Lee ◽

Jung Mi Kwon ◽

Seung-Hyun Nam ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Growth ◽

Cell Line ◽

Pertussis Toxin ◽

Mtt Assay ◽

Inhibitory Effect ◽

Promyelocytic Leukemia ◽

Erk Pathway ◽

Nb4 Cells ◽

Signaling Mechanisms

Abstract There is abundant evidence that S1P can function as a second messenger important for regulation of calcium homeostasis, cell growth, and suppression of apoptosis. In many cases, the intracellular level of S1P and ceramide, another important sphingolipid metabolite associated with cell death and cell growth arrest, coordinately determine cell fate. N, N-dimethylsphingosine(DMS) potentiates TNF- and FasL- induced apoptosis in the human acute leukemia jurkat, U937 and HL-60 cell line, which suggests that combining DMS with cytotoxic drugs might be a useful chemotherapeutic approach. In this study, we investigated the role of S1P on proliferation, survival and its signaling mechanisms on the NB4 cell, the human acute promyelocytic leukemia cell line, which has chromosomal abnormality, t(15:17). NB4 cells were exposed to S1P at various concentrations (1, 5, 10 μM) for 48 hours, and then the cell growth was determined by MTT assay. We studied whether NB4 cells have S1P receptors or not. To investigate the signaling mechanisms of S1P on the NB4 cell, we used MAP kinase inhibitors and a PI3K inhibitor including PD98059, U0126 (specific ERK pathway inhibitor), SB203580 (specific p38 pathway inhibitor), and LY294002 (specific PI3K pathway inhibitor). We also examined the effect of pertussis toxin (PTX), a Gi protein inhibitor, on the proliferation of NB4 cells after S1P treatment. RT-PCR analysis revealed a putative S1P receptor, Edg-3 mRNA expressed in NB4 cells. In the MTT assay, S1P inhibited cell proliferation in a dose-dependent manner. At 10 μM, NB4 cell proliferation was most inhibited. In addition, we found that the inhibitory effect of S1P on the NB4 cell proliferation was inhibited by PD98059, U0126, and PTX. However, SB203580 and LY294002 had not caused an inhibitory effect of S1P on the NB4 cell proliferation. In contrast to previous knowledge that S1P increases the survival of leukemic cells because apoptosis is prevented by caspase inactivation, our data suggests that S1P inhibits NB4 cell proliferation, through ERK pathway activation, not p38 nor JNK pathways. In addition, the pertussis toxin(PTX)-sensitive GTP-binding protein-coupled receptor, Edg-3, seems to be involved in the antiproliferative signaling of S1P to the NB4 cell. Understanding the signaling mechanisms of anti-proliferation by S1P can uncover new therapeutic targets for APL and the results of this study warrant further investigation on synergism of S1P with known therapeutic agent, ATRA and Arsenic trioxide on APL cells.

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Direct inhibitory effect of flaxseed on porcine ovarian granulosa cell functions

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2018-0547 ◽

2019 ◽

Vol 44 (5) ◽

pp. 507-511

Author(s):

Aneta Štochmal’ová ◽

Abdel Halim Harrath ◽

Saleh Alwasel ◽

Alexander V. Sirotkin

Keyword(s):

Cell Proliferation ◽

Granulosa Cells ◽

Inhibitory Effect ◽

Ovarian Cell ◽

Cell Functions ◽

Ovarian Granulosa Cell ◽

Igf I ◽

Direct Inhibitory Effect ◽

Reproductive Processes ◽

Flaxseed Extract

Flaxseed is useful as a functional food and alternative medicine owing to its beneficial health effects. Its action on ovarian cell functions and interrelationships with the upstream hormonal regulators remain unknown. Our aim was to examine the direct influence of flaxseed extract on basal porcine ovarian functions (proliferation, apoptosis), leptin release, and response to insulin-like growth factor I (IGF-I). First, we examined the effect of flaxseed extract on the accumulation of proliferation (PCNA) and apoptosis (Bax) markers and on leptin release in cultured porcine ovarian granulosa cells. Next, granulosa cells were cultured with IGF-I with and without flaxseed extract and analyzed for PCNA and Bax accumulation by quantitative immunocytochemistry and for leptin release by radioimmunoassay. Flaxseed decreased the accumulation of PCNA and increased that of Bax at all doses and reduced leptin output at 100 μg/mL. In contrast, IGF-I promoted PCNA accumulation and suppressed Bax. Flaxseed did not modify IGF-I action on these parameters. Thus, we showed that flaxseed influences porcine reproductive processes, having a direct effect on the ovary and the ability to affect ovarian cell proliferation, apoptosis, and leptin release. Furthermore, we confirmed the pro-proliferative and antiapoptotic actions of IGF-I but showed that flaxseed action on ovarian cell proliferation and apoptosis is not due to changes in the cell response to IGF-I. The potential direct anti-reproductive action of flaxseed needs to be considered during its application in nutrition, medicine, and animal production.

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Transient expression of interleukin 2 receptors. Consequences for T cell growth.

Journal of Experimental Medicine ◽

10.1084/jem.158.6.1895 ◽

1983 ◽

Vol 158 (6) ◽

pp. 1895-1911 ◽

Cited By ~ 388

Author(s):

D A Cantrell ◽

K A Smith

Keyword(s):

Cell Proliferation ◽

T Cells ◽

T Cell ◽

Cell Growth ◽

Interleukin 2 ◽

Flow Cytometric Analysis ◽

Receptor Expression ◽

T Cell Proliferation ◽

Immune Stimulation ◽

T Cell Growth

T lymphocyte mitosis results from the interaction of interleukin 2 (IL-2) with specific receptors that appear only after appropriate immune stimulation. To assess the potential role of IL-2 receptor levels in determining the rate and magnitude of T cell proliferation, the expression of IL-2 receptors by lectin-stimulated human peripheral blood T cells was examined and correlated with T cell growth. Using biosynthetically radiolabeled IL-2 and anti-Tac, a monoclonal antibody that blocks IL-2 receptor binding, IL-2 receptors were found to accumulate slowly and asynchronously among lectin-stimulated T cells and to precede the onset of DNA synthesis. Moreover, a critical threshold of IL-2 receptor density appeared to be required before the commitment to cell cycle progression, as analyzed quantitatively by tritiated thymidine incorporation and flow cytometric analysis of cellular DNA content. Once maximal IL-2 receptor expression occurred, continued proliferation was IL-2 concentration dependent as assessed using homogenous immunoaffinity-purified IL-2. Upon removal of the activating lectin, IL-2 receptor levels progressively declined, and, in parallel, the rate of proliferation diminished. The decay of IL-2 receptors could not be attributed to IL-2-mediated down-regulation. Instead, renewed IL-2 receptor expression was dependent upon the reintroduction of the initial activating signal. Repetitive exposure to lectin resulted in a more rapid reexpression of maximal IL-2 receptor levels, which was then followed by an accelerated resumption of proliferation. Thus, the extent of T cell proliferation after immune stimulation depends upon the interplay of the IL-2 concentration available and the density of IL-2 receptors expressed, both of which are ultimately determined by antigen/lectin stimulation. The awareness of the transience and the antigen/lectin dependence of IL-2 receptor expression, together with the capacity to monitor T cell cultures for IL-2 receptor levels, should facilitate the initiation and maintenance of cloned, antigen-specific T cells in long-term culture. In addition, these findings suggest that, in vivo, the rapidity of acquisition of maximum IL-2 receptor levels by activated T cells and the duration of IL-2 receptor expression may well direct the magnitude of T cell clonal expansion and resultant immune responses.

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Possible role of the systemic inflammatory reaction in defining tumor responder vs. nonresponder in cancer macrobead therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.572 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 572-572

Author(s):

Barry H. Smith ◽

Zoe Padua Andrada ◽

Angelica Nazarian ◽

Allyson J. Ocean ◽

Tapan Parikh ◽

...

Keyword(s):

Clinical Trial ◽

Tumor Marker ◽

Inhibitory Effect ◽

Cell System ◽

T Test ◽

Systemic Inflammatory Reaction ◽

Direct Inhibitory Effect ◽

A Cell ◽

Early Tumor ◽

Induced Changes

572 Background: Peritoneal implantation of mouse renal adenocarcinoma cell-containing (RENCA) Macrobead (MB) represents a cell-system-based approach to the treatment of advanced, mCRC that has been evaluated to date in Phase IIa trials. The data indicate that there are “responders” (R) and “non-responders”(NR) as reflected in overall survival (OS), where “response” is defined as a >20% decrease in either/both CEA or CA19-9 during the first 30 days after MB implantation. We analyzed whether the “response” is due to a post-implant systemic inflammatory response (SIR) or rather a direct inhibitory effect of the MB. Methods: Thirty-four treatment-resistant mCRC patients (pts) were implanted laparoscopically at least once with RENCA MB. Pts were considered R (n=25), or NR (n=9), based on tumor marker responses within the first 30 days. CRP, IL-6, TNF-alpha, and ESR, as measures of SIR, were measured at Day 14 and 30. Results: All 34 pts showed SIR to MB implantation, as indicated by transient rises in CRP, IL-6, TNF-a, and ESR. Baseline CRP values (R, mean 3.24+/-4.39 vs. NR, 2.96+/-3.43; t-test, p=0.86), Day 14 CRP values (R, mean 20.97 +/- 7.21 vs. NR, 14.5+/-8.78; t-test, p=0.04), Day 30 CRP values (R, mean 8.21+/-5.43 vs. NR, 10.76+/-6.92; t-test, p=0.27) and mean changes in IL-6 (baseline p=0.28; Day 14 p=0.36; Day 30 p=0.54), TNF-a (baseline p=0.37; Day 14 p=0.32; Day 30 p=0.29) did not show statistically significant differences between R and NR groups. Conclusions: Data suggest that early tumor marker decreases in R of RENCA MB are likely not due to the induced SIR, but rather a possibly direct anti-tumor-cell effect by factors released by MB. This supports the importance of the MB-induced changes in the MEF-2 pathway in the target colorectal cancer cell/tumor reported previously. Studies of clinical efficacy of MB continue in a Phase IIb clinical trial. Clinical trial information: NCT01053013.

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Inhibitory effect of trapidil on human meningioma cell proliferation via interruption of autocrine growth stimulation

Journal of Neurosurgery ◽

10.3171/jns.1993.78.3.0463 ◽

1993 ◽

Vol 78 (3) ◽

pp. 463-469 ◽

Cited By ~ 33

Author(s):

Tomoki Todo ◽

Eric F. Adams ◽

Rudolf Fahlbusch

Keyword(s):

Cell Proliferation ◽

Growth Factor ◽

Cell Growth ◽

Dna Synthesis ◽

Conditioned Medium ◽

Inhibitory Effect ◽

Maximum Effect ◽

Content Type ◽

Mitogenic Stimulation ◽

Meningioma Cell

✓ In a previous study, the authors demonstrated that meningioma cells secrete platelet-derived growth factor (PDGF)-like molecules that stimulate their own growth in an autocrine manner. Based on that finding, a study was undertaken to examine the effect of trapidil, a drug known to have an antagonistic action against PDGF, on cell proliferation of human meningiomas in culture. Trapidil showed a dose-dependent inhibition of meningioma cell proliferation in the absence of any exogenous mitogenic stimulation. The maximum effect was observed at a concentration of 100 µg/ml, with the decrease in cell growth ranging from 16% to 54% compared to control samples. Trapidil similarly inhibited the basal deoxyribonucleic acid (DNA) synthesis assessed by [3H]-thymidine incorporation in three of seven meningiomas. While the conditioned medium generated from meningioma cells remarkably stimulated the proliferation of meningioma cells (166% to 277% of control), this effect was strikingly inhibited by the addition of trapidil. Trapidil also inhibited conditioned medium-stimulated DNA synthesis, even when there was no effect on basal DNA synthesis. Furthermore, trapidil significantly inhibited the epidermal growth factor (EGF)-stimulated proliferation of meningioma cells. This inhibitory effect on EGF-stimulated cell proliferation was also observed in nontumorous fibroblasts, demonstrating that trapidil is not an antagonist specific to PDGF. The addition of trapidil (30 µg/ml) in combination with bromocriptine (1 µM) showed an additive inhibitory effect on the meningioma cell growth compared to trapidil or bromocriptine alone. The overall results suggest that trapidil exhibits an inhibitory effect on meningioma cell proliferation through blocking the mitogenic stimulation induced by autocrine or exogenous growth factors, and may be considered as a possible new approach to the medical treatment of meningiomas.

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Inhibitory effect of dihydrotestosterone on human thyroid cell growth

Journal of Endocrinology ◽

10.1677/joe.0.1510185 ◽

1996 ◽

Vol 151 (2) ◽

pp. 185-194 ◽

Cited By ~ 19

Author(s):

R Rossi ◽

M C Zatelli ◽

P Franceschetti ◽

I Maestri ◽

E Magri ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Growth ◽

Primary Cultures ◽

Inhibitory Effect ◽

Human Thyroid ◽

Growth Fraction ◽

Thyroid Cell ◽

Mrna Levels ◽

Follicular Cells ◽

Thyroid Follicular Cells

Abstract Sex steroid-binding activities have been identified by several authors in normal and pathological thyroids and the expression of the canonic androgen receptor (AR) has recently been demonstrated in human thyroid follicular cells. In order to assess what influence, if any, androgen exposure has on thyroid cell growth, the effect of dihydrotestosterone (DHT) on [3H]thymidine (thy) incorporation and cell proliferation was investigated in thyroid follicular cells in vitro. In a primary culture of goitrous cells, DHT induced a significant reduction of [3H]thy incorporation at concentrations ranging from 10−12 to 10−8 m, with a more pronounced effect at 10−9 m. At this concentration, the inhibitory effect was evident after both 24 and 48 h of treatment and in various types of primary thyroid cell cultures. In goitrous cells, the DHT-induced decrease of [3H]thy was associated with a reduction of expression of the proliferation-associated nuclear Ki-67 antigen, a protein commonly used to assess cell growth fraction. In TPC cells, an AR-positive thyroid papillary carcinoma cell line, DHT at concentrations between 10−12 and 10−8 m significantly decreased the growth rate. DHT (10−9 m) produced an approximately 50–60% inhibition of cell proliferation and the antiandrogen cyproterone acetate was capable of reversing such effects. The DHT-induced reduction of TPC cell proliferation was associated with a significant reduction of c-myc RNA levels. Thyroperoxidase mRNA levels and thyroglobulin production were not reduced by androgen in primary cultures of goitrous cells. In conclusion, our results indicated that androgens may have a role in this gland by reducing the proliferation, but not the function, of follicular cells. Journal of Endocrinology (1996) 151, 185–194

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Dual Effects of N,N-dimethylformamide on Cell Proliferation and Apoptosis in Breast Cancer

Dose-Response ◽

10.1177/1559325817744450 ◽

2017 ◽

Vol 15 (4) ◽

pp. 155932581774445 ◽

Cited By ~ 4

Author(s):

Jihong Zhang ◽

Daibing Zhou ◽

Lingyun Zhang ◽

Qunbo Lin ◽

Weimin Ren ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cell Growth ◽

Inhibitory Effect ◽

High Dose ◽

Dependent Manner ◽

Cyclin E1 ◽

Proliferation And Apoptosis ◽

Dose Dependent ◽

Mcf 7

N,N-dimethylformamide (DMF) has been widely used as an organic solvent in industries. DMF is a potential medication. However, the antitumorigenic role of DMF in breast cancer remains unclear. Here, we examined dose-dependent effects of DMF on proliferation and apoptosis in breast cancer MCF-7 and nontumorous MCF-12A cells. We found that DMF had a growth inhibitory effect in MCF-12A cells in a dose-dependent manner. By contrast, however, DMF had dual effects on cell proliferation and apoptosis in MCF-7 cells. DMF at a high dose (100 mM) significantly inhibited MCF-7 cell growth while at a low dose (1 mM) significantly stimulated MCF-7 cell growth (both P < .05). The inhibitory effect of DMF on cell proliferation was accompanied by the decrease of cyclin D1 and cyclin E1 protein expression, leading to the cell cycle arrest at the G0/G1 phase. Furthermore, a high-dose DMF significantly increased the number of early apoptotic cells by increasing cleaved caspase-9 and proapoptotic protein Bax expression and decreased the ratio of Bcl-xL/Bax ( P < .01). Thus, our data demonstrated for the first time that DMF has dual effects on breast cancer cell behaviors depending upon its dose. Caution must be warranted in determining its effective dose for targeting breast cancer.

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Effects of oestradiol benzoate (OeB) and human chorionic gonadotrophin (hCG) on the testes and accessory sex glands of the rat

Acta Endocrinologica ◽

10.1530/acta.0.0960273 ◽

1981 ◽

Vol 96 (2) ◽

pp. 273-280 ◽

Cited By ~ 1

Author(s):

Mridula Chowdhury ◽

Robert Tcholakian ◽

Emil Steinberger

Keyword(s):

Treated Group ◽

Inhibitory Effect ◽

Male Rats ◽

Plasma Testosterone ◽

Control Group ◽

Intact Male ◽

Intact Control ◽

Testosterone Levels ◽

Oestradiol Benzoate ◽

Direct Inhibitory Effect

Abstract. It has been suggested that treatment of intact male rats with oestradiol benzoate (OeB) causes an interference with testosterone (T) production by the testes by a direct inhibitory effect on steroidogenesis. To test this hypothesis, different doses (5, 10 or 25 IU) of hCG were administered concomitantly with 50 μg of OeB to adult intact or hypophysectomized male rats. The testicular and plasma testosterone, and serum hCG levels were determined. The sex accessory weights were recorded. In the intact OeB-treated group of animals, hCG stimulated both the secondary sex organs and plasma testosterone levels above the intact control group. However, in hypophysectomized animals, although plasma testosterone levels increased above that of intact controls, their secondary sex organ weights did not. Moreover, inspite of high circulating hCG levels, the testicular testosterone content and concentration remained suppressed in OeB-treated animals. The reason for such dichotomy of hCG action on OeB-treated animals is not clear at present.

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