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At least 307 records · Page 17Linked to original sources
PubMed1982

Relationship between hepatic cholesterol synthesis and biliary cholesterol secretion in man: hepatic cholesterol synthesis is not a major regulator of biliary lipid secretion.

1. To examine the role of newly synthesized cholesterol as a determinant of bile lipid secretion, both hepatic cholesterol synthesis (as judged by the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, EC 1.1.1.34; HMGCoAR) and steady state biliary cholesterol output were measured in nine patients. 2. HMGCoAR levels varied four fold (9-40 pmol min-1 mg-1) and biliary cholesterol secretion 2.5-fold (0.60-1.15 mumol h-1 kg-1) but there was no correlation between these two variables (r = 0.18; P greater than 0.05) nor between biliary bile acid output and HMGCoAR activity (r = 0.34; P greater than 0.05). 3. There was, however, a linear relationship between bile acid and phospholipid secretion (r = 0.77; P less than 0.001) and between bile acid and cholesterol secretion (r = 0.69; P less than 0.05). 4. These results suggest that HMGCoAR activity is not a major determinant of cholesterol secretion nor at these secretion rates is HMGCoAR activity related to bile acid return to the liver.

Bile Acids and Salts↗
PubMed1999

Pilocarpine-induced cholinergic sweat secretion compared with emotional sweat secretion in atopic dermatitis.

We studied pilocarpine-induced cholinergic sweating, emotional sweating and sympathetic reflex sweating in atopic dermatitis (AD) patients. Secreted sweat was measured both with equipment that continuously records sweat rate and with a filter paper method that measures sweat weight absorbed. Comparison of the two methods revealed that the filter paper method underestimated the sweat secretion in AD patients. While AD patients showed no significant abnormalities in emotional sweating and sympathetic reflex sweating, the duration of pilocarpine-induced sweating was prolonged. The time from the maximal sweat rate until the sweat rate fell to half of the maximal rate was significantly longer in AD patients than in control subjects. In contrast, the time from the beginning of sweat secretion until the maximal sweat rate was not significantly different between AD patients and control subjects. There was no significant difference between AD patients and control subjects in sweat volume secreted in 20 min after pilocarpine iontophoresis. In AD patients, the total sweat volume secreted after pilocarpine iontophoresis was greater than in control subjects, although not significantly. These results suggest that the system of deactivation of pilocarpine-induced sweat secretion is impaired in AD patients whereas the activation system is not altered.

Adult↗
PubMed2001

Differences in arginine vasotocin gene transcripts and cortisol secretion in trout with high or low endogenous melanin-concentrating hormone secretion.

Previous studies on trout suggest that melanin-concentrating hormone (MCH) acts at both hypothalamic and pituitary levels to restrain the release of adrenocorticotropic hormone and hence cortisol during stress. Using in situ hybridization, the present work examined whether high rates of MCH secretion were associated with changes in the synthesis of arginine vasotocin (AVT), one of the corticotropin secretogogues. It also examined whether high endogenous MCH secretion restrains cortisol secretion during intense as well as mild stress, and how exogenous MCH affects the rise in plasma cortisol following injection stress. Trout were reared in black- or white-coloured tanks for 1 year or more to achieve maximal differences in MCH secretion. Following a mild stress, cortisol secretion was greater in black-reared fish with low MCH secretion which is in line with previous findings but, following a more severe stress, plasma cortisol concentrations were similar in the two groups. Injection of MCH into black-adapted fish restrained the stress-induced rise in plasma cortisol concentration during the first hour but did not affect final cortisol values. In two separate experiments, AVT mRNA levels were significantly lower in the hypothalamus of black-reared fish. Possible explanations for this include a greater negative-feedback restraint by cortisol, which is likely to rise higher in black-adapted fish during the moderate, daily stresses of aquarium life; or the possibility that exposure to a white background may be psychologically stressful, stimulating AVT transcription. The possibility that MCH directly stimulates AVT transcription cannot be excluded but seems less likely. The results suggest that while MCH may restrain the release of hypothalamo-pituitary stress hormones under moderately stressful conditions, it does not restrain AVT synthesis.

Animals↗
PubMed2002

SpiC is required for secretion of Salmonella Pathogenicity Island 2 type III secretion system proteins.

Replication of Salmonella typhimurium in host cells depends in part on the action of the Salmonella Pathogenicity Island 2 (SPI-2) type III secretion system (TTSS), which translocates bacterial effector proteins across the membrane of the Salmonella-containing vacuole (SCV). We have shown previously that one activity of the SPI-2 TTSS is the assembly of a coat of F-actin in the vicinity of bacterial microcolonies. To identify proteins involved in SPI-2 dependent actin polymerization, we tested strains carrying mutations in each of several genes whose products are proposed to be secreted through the SPI-2 TTSS, for their ability to assemble F-actin around intracellular bacteria. We found that strains carrying mutations in either sseB, sseC, sseD or spiC were deficient in actin assembly. The phenotypes of the sseB-, sseC- and sseD- mutants can be attributed to their requirement for translocation of SPI-2 effectors. SpiC was investigated further in view of its proposed role as an effector. Transient expression of a myc::SpiC fusion protein in Hela cells did not induce any significant alterations to the host cell cytoskeleton, and failed to restore actin polymerization around intracellular spiC- mutant bacteria. However, the same protein did complement the mutant phenotype when expressed from a plasmid within bacteria. Furthermore, spiC was found to be required for SPI-2 mediated secretion of SseB, SseC and SseD in vitro. An antibody against SpiC detected the protein on immunoblots from total cell lysates of S. typhimurium expressing SpiC from a plasmid, but it was not detected in secreted fractions after exposure of cells to conditions that result in secretion of other SPI-2 effector proteins. Investigation of the trafficking of SCVs containing a spiC- mutant in macrophages revealed only a low level of association with the lysosomal marker cathepsin D, similar to that of wild-type bacteria. Together, these results show that SpiC is involved in the process of SPI-2 secretion and indicate that phenotypes associated with a spiC- mutant are caused by the inability of this strain to translocate effector proteins, thus calling for further investigation into the function(s) of this protein.

Actins↗
PubMed1996

Basal and pulsatile secretion of human luteinizing hormone--new methods for the analysis of endocrine secretion processes.

Serum concentrations of hormones show typical time-dependent patterns. The diurnal course of the serum concentrations of the luteinizing hormone (LH) was assessed in 35 healthy females monitoring individual concentrations every ten minutes for 24 hours during the follicular phase of their menstrual cycle. Based on these in vivo data, a mathematical procedure was developed for calculation of the momentary hormone secretion rate of an endocrine gland from the time course of the hormone serum concentrations. By means of this procedure, we were able to define the complete 24 hours secretion pattern of LH, including the fact, that basal and pulsatile secretion could be separated from each other in an objective manner. It is possible to calculate the total amount of LH which is secreted per LH-pulse and the basal LH-secretion rate. Two methods were developed to define the time of the onset of an LH-pulse with a preselected probability. Describing the hormonal secretion pattern with a mathematical model provides the basis for therapeutic application of these methods to program implantable hormone-pumps for the therapy of glandular insufficiency.

Adult↗
PubMed2001

Directed polar secretion of protease from single cells of Vibrio cholerae via the type II secretion pathway.

Bacteria have long been thought of as little more than sacks of homogeneously distributed enzymes. However, recent cytological studies indicate that bacteria are compartmentalized with proteins involved in processes such as cell division, motility, chemotaxis, and development located at distinct sites. We have used the green fluorescent protein as a reporter to determine the cellular distribution of the extracellular protein secretion (eps)-encoded type II secretion complex responsible for extracellular secretion of cholera toxin and hemagglutinin/protease in Vibrio cholerae. Real-time monitoring of green fluorescent protein fused to EpsM in living cells indicated that, like the single polar flagellum, the Eps complex is located at the old pole after cell division. Eps-dependent protease secretion was also visualized in single cells by fluorescence microscopy by using intramolecularly quenched casein. This analysis demonstrated that active protease secretion is focused at the poles and colocalizes with the site of the polar Eps apparatus. These results suggest that the type II secretion complex is responsible for directed delivery of virulence factors during cholera pathogenesis.

Bacterial Proteins↗
PubMed1998

A cloned Erwinia chrysanthemi Hrp (type III protein secretion) system functions in Escherichia coli to deliver Pseudomonas syringae Avr signals to plant cells and to secrete Avr proteins in culture.

The Hrp (type III protein secretion) system is essential for the plant parasitic ability of Pseudomonas syringae and most Gram-negative bacterial plant pathogens. AvrB and AvrPto are two P. syringae proteins that have biological activity when produced via heterologous gene expression inside plant cells or when produced by Hrp+ bacteria. Avr-like proteins, presumably injected by the Hrp system on bacterial contact with plant cells, appear to underlie pathogenic interactions, but none has been observed outside of the bacterial cytoplasm, and identifying novel genes encoding them is tedious and uncertain without a phenotype in culture. Here we describe a cloned Hrp secretion system that functions heterologously in Escherichia coli to secrete AvrB and AvrPto in culture and to promote AvrB and AvrPto biological activity in inoculated plants. The hrp gene cluster, carried on cosmid pCPP2156, was cloned from Erwinia chrysanthemi, a pathogen that differs from P. syringae in being host promiscuous. E. coli DH5alpha carrying pCPP2156, but not related Hrp-deficient cosmids, elicited a hypersensitive response in Nicotiana clevelandii only when also expressing avrB in trans. The use of pAVRB-FLAG2 and pAVRPTO-FLAG, which produce Avr proteins with a C-terminal FLAG-epitope fusion, enabled immunoblot detection of the secretion of these proteins to E. coli(pCPP2156) culture media. Secretion was Hrp dependent, occurred without leakage of a cytoplasmic marker, and did not occur with E. coli(pHIR11), which encodes a functional P. syringae Hrp system. E. coli(pCPP2156) will promote investigation of Avr protein secretion and systematic prospecting for the effector proteins underlying bacterial plant pathogenicity.

Bacterial Proteins↗
PubMed2002

Modular arrangement and secretion of a multidomain serine protease. Evidence for involvement of proline-rich region and N-glycans in the secretion pathway.

The Limulus Factor C (FC), a multidomain glycoprotein that binds bacterial endotoxin with high affinity, belongs to the serine protease family of the complement and blood coagulation cascade. Here, we provide compelling evidence for the importance of modular arrangement and relevance of the proline-rich region (PRR) and N-glycosylation to the secretion and function of FC. We propose that PRR could be a universal conformational domain that regulates protein folding and targeting. FCs lacking PRR preceding the serine protease domain, were localized intracellularly. Misfolded conformers of the intracellular FCs were more susceptible to trypsin digestion. Glycosylation inhibition studies indicate that the presence but not the exact structure of the N-glycans affects the secretion of FC, although the complexity of glycosylation may influence its endotoxin-induced proteolytic cleavage with resultant enzymatic activity. Disruption of specific N-glycan sites at positions 740, 767, and 912, downstream of the PRR, at or near the serine protease domain, blocks its secretion. Co-expressed molecular chaperones like canine calnexin associates with glycosylated FCs to increase its solubility and secretion level but did not alter their expression profiles. Our results clearly demonstrate that the folding and secretion of a multidomain serine protease like FC are determined by its modular domain arrangement and site-specific N-glycans. The secreted FCs containing the N-terminal portion of FC are able to detect lipopolysaccharide with high sensitivity. We also identified the lectin-like and sushi 4 domains to contribute to the binding of lipopolysaccharide.

Amino Acid Sequence↗
PubMed1998

Induction of type III secretion in Shigella flexneri is associated with differential control of transcription of genes encoding secreted proteins.

Shigella, the etiological agent of human bacillary dysentery, invades the colonic epithelium where it induces an intense inflammatory response. Entry of Shigella into epithelial cells involves a type III secretion machinery, encoded by the mxi and spa operons, and the IpaA-D secreted proteins. In this study, we have identified secreted proteins of 46 and 60 kDa as the products of virA and ipaH9.8, respectively, the latter being a member of the ipaH multigene family. Inactivation of virA did not affect entry into epithelial cells. Using lacZ transcriptional fusions, we found that transcription of virA and four ipaH genes, but not that of the ipaBCDA and mxi operons, was markedly increased during growth in the presence of Congo red and in an ipaD mutant, two conditions in which secretion through the Mxi-Spa machinery is enhanced. Transcription of the virA and ipaH genes was also transiently activated upon entry into epithelial cells. These results suggest that transcription of the virA and ipaH genes is regulated by the type III secretion machinery and that a regulatory cascade differentially controls transcription of genes encoding secreted proteins, some of which, like virA, are not required for entry.

Amino Acid Sequence↗
PubMed1992

Secretion of lipoprotein cholesterol by perfused livers from rabbits hypo- or hyperresponsive to dietary cholesterol: greater dietary cholesterol-induced secretion in hyperresponsive rabbits.

In two inbred strains of rabbits with high or low response of plasma cholesterol to dietary cholesterol, secretion of lipoprotein cholesterol by perfused livers was determined. The perfused rabbit livers secreted cholesterol into the perfusate at essentially constant rates between 30 and 120 min of perfusion. Most of the secreted cholesterol resided in VLDL. Addition of cholesterol to the diet of the donor rabbits caused a higher cholesterol:triglyceride ratio of lipoproteins secreted by the perfused liver. Such a rise was also seen in the plasma lipoproteins of cholesterol-fed rabbits. Plasma and perfusate lipoproteins differed in that the former had a higher cholesterol:triglyceride ratio. Cholesterol feeding produced a higher output of lipoprotein cholesterol by the perfused liver, the increment being greater in hyper- than in hyporesponders. Cholesterol-fed hyperresponders had higher liver cholesterol concentrations than their hyporesponsive counterparts. There was a direct relationship between the rise of liver cholesterol concentrations and the rise of hepatic secretion of lipoprotein cholesterol; this relationship was identical for hypo- and hyperresponders. We conclude that the higher cholesterolemic response to cholesterol feeding in the hyperresponders, when compared with the hyporesponders, can be explained, at least partly, by a greater cholesterol-induced hepatic secretion of lipoprotein cholesterol.

Animals↗
PubMed2005

Bacterial type two secretion system secreted proteins: double-edged swords for plant pathogens.

The type two secretion system (T2S) is important for virulence of a number of gram-negative bacterial plant pathogens. Most of the T2S-secreted proteins that have been characterized to date are involved in degrading different components of plant cell walls. Functional redundancy appears to exist among T2S-secreted proteins because significant effects on virulence are observed only in strains in which multiple secreted proteins are mutated. Several T2S-secreted proteins have been shown to induce plant defense responses, including hypersensitive response-like reactions. Bacterial pathogens can suppress these defense responses, and recent results indicate that suppression is mediated through the type three secretion system.

Bacteria↗
PubMed1989

In vitro-perifused rat testes secrete beta-endorphin and dynorphin: their effect on testosterone secretion.

Leydig cells of many species synthesize and secrete opioid peptides, but the Sertoli and possibly the peritubular cells are the only intratesticular cells having opiate receptors. It is known that Sertoli and peritubular cells can modify the secretion of testosterone from Leydig cells. To test the hypothesis that testicular opioid peptides participate in a Leydig-Sertoli-peritubular-Leydig cell feedback loop that can regulate the intratesticular concentration of testosterone, we have developed a method for the in vitro perifusion of rat testicular fragments in which the intratesticular structure and thus the paracrine feedback loop remains intact. Our data show that both immunoreactive (IR)-beta-endorphin and IR-dynorphin were present in the testicular perifusion effluent; gel chromatography of pooled perifusion effluent show that the bulk of the secreted IR-beta-endorphin had the apparent mol. wt. of synthetic rat beta-endorphin whereas most of the secreted IR-dynorphin was composed of smaller than 4000 mol. wt. forms. On the other hand, the bulk of IR-dynorphin present in rat testicular tissue homogenates eluted in two higher mol. wt. peaks. The effect of mu and kappa opioid agonists and naloxone (a universal opioid antagonist) on both basal and gonadotropin-stimulated testosterone secretion from perifused testicular fragments was then examined; no stimulatory or inhibitory effect of the opioid receptor agonists or naloxone was found on basal and gonadotropin-stimulated testosterone secretion. Parallel experiments with Leydig cells in culture gave similar results.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Regulation of luteinizing hormone-releasing hormone (LHRH) secretion by melatonin in the ewe. I. Simultaneous delayed increase in LHRH and luteinizing hormone pulsatile secretion.

This study was performed to test the hypothesis that a short-day-like melatonin treatment would induce simultaneous stimulations of LHRH and LH secretion. Simultaneous serial samples of jugular and portal blood to assay LH and LHRH, respectively, were carried out at three different periods according to the expected changes in LH secretion. Twenty-six ovariectomized ewes bearing a subcutaneous implant of estradiol and exposed to a long-day photoperiod (16L:8D) received s.c. implants of melatonin on Day 0. LHRH and LH pulsatile secretion was studied in the first group during inhibition of LH secretion by long days (on Day -1, n = 6). A second group (n = 9) was sampled on Day 39. Moreover, seven animals from this group were sampled on Day 46 to focus on the beginning of LH increase. The third group (n = 6) was sampled during maximal LH secretion (Day 74, n = 6). A fourth group (n = 5) composed of noncannulated animals was sampled for LH secretion only as a control for the effects of surgical procedures. On each occasion, blood was collected every 10 min for 6 h. Between Day -1 and Day 39, LHRH pulse frequency was low and did not differ. In the same animals, this value became 2.5-fold higher between Day 39 and Day 46. Finally, on Day 74, LHRH pulse frequency was about 6-fold higher than on Day -1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Regulation of luteinizing hormone-releasing hormone (LHRH) secretion by melatonin in the ewe. II. Changes in N-methyl-D,L-aspartic acid-induced LHRH release during the stimulation of luteinizing hormone secretion by melatonin.

Injection of N-methyl-D,L-aspartic acid (NMDA), a glutamatergic agonist, cause an acute release of LH. The amount of LH released is modulated by photoperiod in sheep; it is larger in animals in which reproductive activity has been inhibited by long days than in those photostimulated by short days. The purpose of the present experiment was to determine whether this effect of photoperiod on LH response to NMDA is mediated by melatonin and whether it reflects a change in the amount of LHRH released in response to NMDA. Twenty-one ovariectomized ewes, bearing an s.c. implant of estradiol and kept in long days (16L:8D), received s.c. implants of melatonin on Day 0. The effect of a single injection of NMDA (5 mg/kg i.v.) on LHRH and simultaneous LH secretion was studied at three different periods of the stimulation of LH secretion by the melatonin treatment: first, during inhibition of LH secretion by long days (on Day -1, n = 6); secondly, during the onset of the LH increase (on Day 39, n = 9); and thirdly, during maximum LH secretion (on Day 74, n = 6). The stimulation of LHRH secretion by administration of NMDA was characterized by a large and long increase in LHRH concentration on Day -1 and Day 39. There was no significant difference between these two periods in terms of duration and amplitude of the LHRH release. On Day 74, the stimulation was much shorter than on Day -1 and Day 39 and was followed by a phase of decreased pulsatility of LHRH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Atrial natriuretic peptide suppresses isoprenaline and dibutyryl cyclic adenosine monophosphate-induced cell growth in cultured renin-secreting human nephroblastoma cells. Comparison with forskolin-induced renin secretion.

OBJECTIVE: Renin secretion in response to long-term exposure to isoprenaline, dibutyryl cyclic adenosine monophosphate (dbcAMP), forskolin and atrial natriuretic peptide (ANP) was measured in cultured human nephroblastoma cells. METHODS: Human nephroblastoma cells in culture were treated long-term (1-12 days) with isoprenaline, dbcAMP or forskolin, alone or in combination with ANP; renin release and cell growth were studied. RESULTS: The increase in renin output caused by isoprenaline and dbcAMP could be accounted for by stimulation of cell growth. The effect of isoprenaline was blocked by propranolol. Forskolin stimulated renin secretion per cell. ANP increased extracellular cyclic guanosine monophosphate and suppressed basal renin output. Suppression of basal renin output was due to a reduced secretion rate per cell, without a change in cell growth. ANP suppressed isoprenaline-induced and dbcAMP-induced renin output by blocking increased cell growth, and forskolin-induced renin output by blocking renin secretion. CONCLUSIONS: These results suggest that beta-receptor agonists and ANP interact within the kidney to control renin secretion, by helping to determine the number of renin-secreting cells.

Atrial Natriuretic Factor↗
PubMed2001

Gender differences in cytokine secretion by human peripheral blood mononuclear cells: role of estrogen in modulating LPS-induced cytokine secretion in an ex vivo septic model.

Clinical studies demonstrate a better outcome of sepsis in females. Elevated estrogen levels and plasma cytokine imbalance occur in septic patients. We propose that gender-different cytokine secretion by the peripheral blood mononuclear cells (PBMCs) in sepsis determines the clinical outcome. A 2 x 10(6) PBMC sample from healthy volunteers (10 males and 10 females) was incubated with 1 ng/mL of lipopolysaccharide (LPS), estradiol (E2; 0, 0.03, 0.3, 3.0, 30 ng/mL), or 1 ng/mL of LPS + E2 (0, 0.03, 0.3, 3.0, 30 ng/ml), and supernatant cytokine levels were measured. Tumor necrosis factor alpha (TNF alpha) and interleukin (IL)-6 production by PBMCs from both sexes was time-dependently stimulated by LPS. At 6 h after LPS challenge, the TNF alpha level of male PBMCs was significantly higher but IL-6 secretion by female PBMCs was higher (two-way ANOVA: P < 0.05). E2 alone stimulated cytokine secretion by male PBMCs. Addition of the same E2 concentration as in sepsis patients' plasma modulated LPS-induced cytokine production. No significant sex differences in LPS-stimulated TNF alpha or IL-6 secretion by PBMCs were found, but IL-10 secretion by male PBMCs was significantly suppressed. This study demonstrated a gender difference in PBMCs responsiveness to LPS and E2 stimulation and E2-modulated cytokine secretion. In this PBMCs model of sepsis, only the supernatant IL-10 level was significantly lower in males. These ex vivo findings may partially explain the mechanism underlying the poorer outcome of male sepsis patients.

Adult↗
PubMed1989

Apparent Inhibition of beta-Fructosidase Secretion by Tunicamycin May Be Explained by Breakdown of the Unglycosylated Protein during Secretion.

Suspension-cultured carrot (Daucus carota) cells synthesize and secrete beta-fructosidase, a glycoprotein with asparagine-linked glycans. Treatment of the cells with tunicamycin completely inhibits the apparent secretion of beta-fructosidase as measured by the accumulation of the radioactive protein in the cell wall or the culture medium. In the past, such a result has been interpreted as an inhibition of secretion by tunicamycin, but we suggest another explanation based on the following results. In the presence of tunicamycin, unglycosylated beta-fructosidase is synthesized and is associated with an endoplasmic-reticulum-rich microsomal fraction. Pulse-chase experiments show that the unglycosylated beta-fructosidase does not remain in the cells and appears to be secreted in the same way as glycosylated beta-fructosidase; however, no radioactive, unglycosylated beta-fructosidase accumulates extracellularly (cell wall or medium). Protoplasts obtained from carrot cells secrete beta-fructosidase protein and activity, and treatment of the protoplasts with tunicamycin results in the synthesis of unglycosylated beta-fructosidase. In the presence of tunicamycin, there is no accumulation of beta-fructosidase activity or unglycosylated beta-fructosidase polypeptide in the protoplast incubation medium. These results are consistent with the interpretation that the glycans of beta-fructosidase are necessary for its stability, and that in these suspension-cultured cells, the unglycosylated enzyme is degraded during the last stage(s) of secretion, or immediately after its arrival in the wall.

Journal Article↗
PubMed1981

Control of gonadotrophin secretion by steroid hormones in castrated male transsexuals. II. Effects of androgens alone and in combination with oestradiol on the secretions of FSH and LH.

Twenty-nine infusions in twenty castrated male transsexual volunteers were carried out over a period of 7 h with subjects lying in the supine position. The effects of different doses of testosterone and its 5 alpha-reduced metabolites as well as the effect of testosterone in combination with oestradiol on gonadotrophin secretion were evaluated. Different and varying degrees of suppression of plasma levels of FSH and LH were observed. The infusions of 2.4 mg testosterone, 5 alpha-androstan-3 alpha-17 beta-diol (3 alpha-diol), 5 alpha-androstan-3 beta-17 beta-diol (3 beta-diol) but not dihydrotestosterone (DHT) caused significant suppression of LH. FSH, on the other hand was not significantly inhibited by the androgens at this rate. At higher doses all four androgens suppressed LH secretion significantly. FSH was similarly suppressed by the androgens except by DHT. A differential effect on FSH and LH secretions was noted with the combined regime of testosterone and oestradiol. The combined regime did not cause a significantly higher degree of FSH suppression compared with either 200 microgram of oestradiol or 12 mg of testosterone infused alone. The level of LH, however, was suppressed to a greater extent than either of the hormones when given alone. The inhibitory effect of testosterone demonstrated in this study could be due to the parent hormone or its 5 alpha-reduced metabolites. Pharmacological doses of testosterone could exert a greater degree of LH suppression through its conversion to oestradiol. It is likely that oestradiol and testosterone act on gonadotrophin secretion through different mechanisms and that they have an additive suppressive effect on the secretion of LH but not FSH. The potencies for the androgens to suppress gonadotrophin secretion can be ranked as: 3 alpha-diol = 3 beta-diol greater than testosterone greater than dihydrotestosterone.

Androgens↗