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Biomedical subjects

W H Moger

Publications and source records attributed to W H Moger.

At least 19 recordsLinked to original sources
PubMed1995

Hormonal responses of male gerbils to stimuli from their mate and pups.

Following copulation and cohabitation with a pregnant female, male gerbils show high levels of parental behavior toward their pups. The initiation of male parental behavior may be the result of neuroendocrine changes induced by cohabiting with the pregnant female or by pup stimuli. Experiment 1 examines the changes in androgen and prolactin levels in male gerbils cohabiting with females over the reproductive cycle. Gerbils were mated and blood samples taken from males for hormone analysis 1, 10, and 20 days after pairing and 3, 10, and 20 days after pups were born. A group of unmated male gerbils served as controls. Plasma prolactin levels of males were elevated throughout the female's pregnancy and lactation periods, but were only statistically significantly higher than those of unmated males 20 days after pups were born. Androgen levels rose during pregnancy and dropped significantly after the birth of the pups. These hormonal changes are similar to those found in males of monogamous birds and differ from those found in males of polygynous rodents such as the rat. Experiment 2 examined the hormonal responses of male and female gerbils to pup replacement after 4 hr of parent-pup separation. Female gerbils showed a significant elevation of prolactin levels 1 hr after pup replacement, but males did not. Males with pups returned showed no difference in androgen levels from males who did not have pups returned. Thus, male gerbils show neuroendocrine changes following long-term cohabitation with their mate and pups, but do not show acute hormone responses to pup removal and replacement. These results indicate that parental males have neuroendocrine changes associated with parental behavior and these differ from the neuroendocrine changes underlying female parental behavior.

Androgens↗
PubMed1992

Apolipoprotein-E messenger RNA in rat ovary is expressed in theca and interstitial cells and presumptive macrophage, but not in granulosa cells.

Apolipoprotein-E (apoE) is a constituent of various lipoproteins and is a ligand for cellular lipoprotein receptors. Unlike most apolipoproteins, apoE is synthesized in peripheral tissues, including those engaged in steroidogenesis. ApoE expression in adrenal cells inhibits cholesterol utilization for steroid synthesis and blocks signal transduction via the protein kinase-A pathway. In cultured ovarian thecal/interstitial cells, exogenous apoE has been shown to inhibit LH-induced androgen synthesis. These findings support a role for apoE as an autocrine or paracrine factor involved in regulating steroidogenesis. In the present study in situ hybridization was used to identify cell types that express apoE mRNA in ovaries from rats with a 4-day estrous cycle, from pregnant rats, from immature rats treated with PMSG to stimulate follicular development, and from PMSG-treated rats that were subsequently administered hCG to stimulate ovulation and luteinization. ApoE mRNA was localized to theca and interstitial cells of follicles in animals at all stages of the estrous cycle as well as in immature rats treated with PMSG. ApoE mRNA was not detected in oocytes, cumulus cells, or granulosa cells. High levels of apoE mRNA also were expressed by localized clusters of presumptive macrophages in atretic follicles and degenerating corpora lutea. This complex pattern of expression may indicate that apoE has multiple functions in the rat ovary. ApoE made by theca and interstitial cells may act locally as an autocrine factor to regulate androgen production. ApoE made in atretic follicles and regressing corpora lutea may serve to facilitate local transport and reutilization of lipid released as these structures degenerate.

Animals↗
PubMed1991

Development of the normal XY male and sex-reversed XXSxr pseudomale mouse epididymis.

XXSxr pseudomale mice (chromosomally XX animals "sex-reversed" by the Sxr factor) develop testes and produce sufficient androgens for masculinization as assessed at the macroscopic level. However, adult XXSxr pseudomales lack the epididymal initial segment (I.S.). In this study prenatal and postnatal epididymal development was examined histologically and biochemically, and it was found that XXSxr pseudomales are indistinguishable from normal XY males up to day 21 of postnatal life. By 25 days postnatally, before the onset of the pubertal androgen surge, the I.S. precursor is evident in normal animals but absent in XXSxr mutants. No major abnormalities were seen in other segments of the XXSxr epididymis. Our data suggest that androgen levels in testis and epididymis are not higher in normal XY males than in XXSxr pseudomale mice of the same age. Inadequate availability of androgens at the target site is unlikely to be the cause of the epididymal abnormality in XXSxr pseudomale mice.

Androgens↗
PubMed1991

Interaction between cyclic nucleotide second messenger systems in murine Leydig cells.

Mouse Leydig cell androgen production can be acutely stimulated by atrial natriuretic factor (ANF) via cyclic guanosine 3',5'-monophosphate (cGMP). This stimulation can approach that seen with high concentrations of luteinizing hormone (LH) acting via cyclic adenosine 3',5'-monophosphate (cAMP). To assess the potential for synergistic interaction between LH/cAMP and ANF/cGMP Leydig cells were co-exposed to ANF and LH or ANF/cGMP and site/type-selective cAMP analogues. Co-exposure to 1 nM ANF and 1 ng/ml LH elicited a synergistic increase in androgen production. Both 500 microM 8-bromo-cGMP and ANF (1.0-2.5 nM) synergized with cAMP analogues selective for either of the two major isoenzymes of protein kinase A. Phosphodiesterase (PDE) inhibition was not involved as inclusion of a PDE inhibitor only augmented the response. It appears that ANF/cGMP may interact cooperatively with LH/cAMP in the stimulatory control of androgen production in the mouse Leydig cell and that the site of synergistic interaction may be the activation of the cAMP-dependent protein kinase.

Animals↗
PubMed1991

Type 1 and 2 isoenzymes of cAMP-dependent protein kinase in Leydig cell steroidogenesis.

This study examined the functional significance of the type 1 (T1) and type 2 (T2) cAMP-dependent protein kinase (PK-A) isoenzymes in androgen production by mouse Leydig cells. Leydig cells were exposed to cAMP analogues selective for either of the two cAMP binding sites on the regulatory subunits of each PK-A isoenzyme. As the two binding sites have been shown to exhibit positive cooperativity, coexposure to the appropriate combination of analogues will synergistically increase androgen production if either T1 or T2 PK-A is present and functional in the cell. We found that both PK-A isoenzymes are present and functionally active, though the T1 kinase predominates. Coexposure to the cAMP analogues and cAMP or luteinizing hormone also synergistically increased androgen production via both isoenzymes while forskolin acted only via the T1 isoenzyme, suggesting that forskolin may instigate cellular events in addition to cAMP synthesis.

Androgens↗
PubMed1991

Evidence for compartmentalization of adenosine 3',5'-monophosphate (cAMP)-dependent protein kinases in rat Leydig cells using site-selective cAMP analogs.

It is generally believed that LH-stimulated steroidogenesis in Leydig cells is via activation of the cAMP second messenger system. The present study used cAMP analogs selective in their binding to the two types of cAMP-dependent protein kinase (PK-A) and/or selective in their binding to the two cAMP-binding sites on the regulatory subunits of PK-A. As the two cAMP-binding sites show positive cooperativity, synergistic increases in androgen production by rat Leydig cells occurred when they were incubated in vitro with analog pairs that selectively activated PK-A type I or II. This confirmed that both types of PK-A are present in Leydig cells and demonstrated that both PK-A types are capable of activating steroidogenesis. Synergistic increases in androgen production were also observed when either a type I selective analog (8-aminohexylamino-cAMP) or a type II selective analog (8-thiomethyl-cAMP) was paired with added cAMP. However, when these analogs were paired with LH or the adenylate cyclase activator forskolin, a synergistic increase in steroidogenesis occurred only with the type I selective analog. These results suggest that PK-A type I is compartmentalized in Leydig cells so that it has preferential access to endogenously produced cAMP.

Animals↗
PubMed1991

Interleukin-1 alpha-induced changes in androgen and cyclic adenosine 3',5'-monophosphate release in adult rat Leydig cells in culture.

Interleukin-1 (IL-1) has been proposed as a paracrine regulator of testicular function. The effect of this cytokine on adult rat Leydig cells in primary culture was investigated. Interstitial cells were purified on a two-step Percoll gradient and cultured in the presence or absence of recombinant human IL-1 alpha (IL-1 alpha). The presence of IL-1 alpha in the culture media resulted in a dose-dependent increase in 24-h basal androgen release (half-maximal effective concentration = 40-50 U/ml). The stimulatory effect of IL-1 alpha peaked on days 3 and 4, and was often still significant after 6 days of culture. Removal of IL-1 alpha was followed by a return of basal androgen release to control levels within 3 days. In contrast, cells treated with IL-1 alpha (100 U/ml) for 3 days released significantly less androgen (per 4 h) in response to 1-100 ng LH/ml than control cells. A similar inhibitory effect on the response to dibutyryl cAMP and pregnenolone was observed. Under basal conditions, IL-1 alpha-treated cells released significantly more cAMP than did control cells. In contrast, the increase in cAMP release seen with LH-stimulated cells was significantly inhibited by treatment with IL-1 alpha. These results suggest that IL-1 alpha has a dual effect on adult rat Leydig cells in culture. It stimulates basal but inhibits LH-induced androgen release with parallel changes in cAMP levels. An additional inhibitory effect appears to lie at the level of the 17 alpha-hydroxylase/C17-20 lyase enzyme.

Androgens↗
PubMed1989

Verification of NB2 lymphoma cell bioassay for the measurement of plasma and pituitary prolactin in the Mongolian gerbil (Meriones unguiculatus).

Serum and pituitary glands were taken from male Mongolian gerbils which had received bromocriptine implants, ether stress or no treatment (controls). Pituitary prolactin (Prl) and growth hormone (GH) mRNA were analyzed by Northern hybridization using rat cDNA probes. Pituitary and plasma Prl content were analyzed with the Nb2 lymphoma cell growth bioassay. These assays were sensitive to the decreases in Prl caused by bromocriptine and the elevation of Prl caused by ether stress. The inhibition of pituitary and plasma Prl levels by bromocriptine correlated with a marked inhibition of pituitary Prl mRNA content. In contrast, levels of GH mRNA did not change with treatment, indicating that gerbil GH does not contribute to the lactogenic activity measured in the Nb2 lymphoma cell bioassay. The results indicate that this bioassay is suitable for the measurement of gerbil pituitary and plasma Prl.

Animals↗
PubMed1988

Constitutive glucose transport in rat Leydig cells and pyruvate support of steroidogenesis.

To facilitate the interpretation of in vitro experiments that use pharmacological agents, such as cytochalasin B, which inhibits glucose transport, an alternative to glucose as an energy source for rat Leydig cells was sought. Pyruvate was superior to glucose as an energy source for the support of steroidogenesis. The concentration of pyruvate required to support half-maximum androgen production was lower than that for glucose (60 +/- 8 versus 478 +/- 87 microM, respectively), and pyruvate supported a higher rate of maximum LH-stimulated androgen production. The latter result suggested that glucose availability can be rate limiting for steroidogenesis in in vitro experiments. The acute regulation of glucose transport was therefore investigated using 2-Deoxy-D-[2,6(3)H]glucose. Uptake of 2-Deoxy-D-[2,6(3)H]glucose by Leydig cells was not affected by insulin, LH, or glucose deprivation, suggesting that it is a constitutive process in these cells.

Androgens↗
PubMed1987

Plasma androgen levels during male parental care in a tropical frog (Eleutherodactylus).

Males of the Puerto Rican frog Eleutherodactylus coqui practice parental care of terrestrial eggs throughout embryonic development (17-26 days). Parental care is associated with marked changes in male behavior, including the cessation of normal calling activity (necessary for mate attraction) and reduction of egg cannibalism. To analyze the relationship between parental behavior and androgens, blood was collected from male frogs in the field and plasma analyzed for total androgens. Parental males had significantly lower androgen levels than both nonparental, calling males, and amplectant (mating) males. The decline in circulating androgens between the sexually active state (calling and mating) and the parental care state was fairly rapid (less than 12 hr). Androgen levels did not differ among parental males at different stages of the parental care period.

Androgens↗
PubMed1986

Catecholamine stimulation of androgen production by rat Leydig cells. Interactions with luteinizing hormone and luteinizing hormone-releasing hormone.

The mechanism(s) of the development of response to catecholamines (CA) by Leydig cells in culture was investigated with the use of primary culture of purified Leydig cells of adult rats. The interactions of a CA agonist, isoproterenol (ISOP), with luteinizing hormone (LH) and a luteinizing hormone-releasing hormone agonist analog (LHRHa) on production of androgen by the Leydig cells were also studied. Cells incubated with ISOP for 3 h increased release of cyclic adenosine 3',5'-monophosphate (cAMP) to similar extents at 0, 3, and 24 h of culture. The beta-agonist did not increase androgen release at 0 h but had a concentration-dependent effect at 3, 24, and 48 h of culture, with maximal effects at 24 h. LH stimulated high increases in production of cAMP and androgen by the cells at 0-24 h of culture. Leydig cell beta-receptors decreased with culture time. Low concentrations but not high levels of LH had additive effects with ISOP on androgen release. ISOP showed a complex interaction with LHRHa on androgen release. Chronic exposure of Leydig cells to LHRHa reduced basal androgen release as well as release of androgen stimulated by ISOP, forskolin, and LH. These studies suggest that the development of response to CA by rat Leydig cells is a postreceptor, postcAMP event and showed that CA can interact with LH or LHRH to regulate Leydig cell function.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Propranolol inhibits the compensatory increase in androgen secretion after unilateral orchidectomy in rats.

Adrenergic antagonists were administered to rats by intratesticular injection at the time of unilateral orchidectomy and 5 h before autopsy, 24 h after surgery. Injections of the beta-receptor antagonist DL-propranolol (0.5 or 1.0 mg/injection) significantly inhibited the increase in the concentration of androgens in testicular vein plasma or interstitial fluid that occurred in unilaterally orchidectomized animals injected with vehicle. DL-Propranolol injections in animals with both testes did not reduce testicular or peripheral androgen concentrations or their increase after hCG administration. Injections of the less potent isomer (+)-propranolol or the alpha-receptor antagonist phentolamine did not inhibit the response to unilateral orchidectomy. It is concluded that the compensatory increase in androgen secretion induced by unilateral orchidectomy is, at least in part, the result of beta-adrenergic stimulation of steroidogenesis.

Androgens↗
PubMed1986

Androgen levels and androgenization in sex-reversed (XXSxr pseudomale) mouse: absence of initial segment of epididymis is independent of androgens.

The XXSxr pseudomale ("sex-reversed") mouse has an apparently normal male phenotype. This is in accordance with Jost's Principle that, in an animal with androgen-producing testes, phenotype will be fully masculinized, irrespective of chromosomal sex. However, the epididymis of this mutant lacks the Initial Segment. Several alternative explanations were proposed. In the present study we examined the primary of these, viz, androgen insufficiency. We studied androgen levels in serum and tissues of the mutant, and we investigated whether injection of exogenous androgens could induce normal development. The XXSxr pseudomale is not deficient in androgens, nor do exogenous additional androgens induce development of the Initial Segment. It would appear that the abnormal genotype acts on the organ phenotype without intervention of androgens.

Androgens↗
PubMed1985

Stimulation and inhibition of Leydig cell steroidogenesis by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate: similarity to the effects of gonadotropin-releasing hormone.

To explore the mechanism of gonadotropin-releasing hormone (GnRH) action on Leydig cell steroidogenesis the effects of a GnRH analog (GnRHa) were compared to those of 12-O-tetradecanoylphorbol 13-acetate (TPA). Both compounds acutely stimulated androgen production 2-4 fold with EC50's of 9 nM (TPA) and 0.2 nM (GnRHa). The effects of TPA and GnRHa were not additive and neither compound acutely altered the luteinizing hormone (LH) concentration-response relationship. After 24 h of exposure to TPA or GnRHa the ability of LH to stimulate androgen production was impaired. The parallel effects of TPA and GnRHa on Leydig cell steroidogenesis suggest that they are acting via similar mechanisms; presumably the activation protein kinase C.

Androgens↗
PubMed1985

Characterization of beta-adrenergic binding sites on rodent Leydig cells.

A radioligand binding technique was used to study beta-adrenergic binding sites on rodent Leydig cells. Beta-Adrenergic binding sites were found on Leydig cells in both the rat and mouse. Binding of [3H]CGP-12177 [4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-3H]benzimidazole-2-one] to purified rat Leydig cells was found to be saturable, temperature and time dependent, stereospecific, and readily reversible by the beta-adrenergic antagonist propranolol. Scatchard analysis revealed the presence of high-affinity sites with an apparent dissociation constant (Kd) of 0.79 +/- 0.22 nM and maximal binding capacity (Bmax) of 1716 +/- 245 sites per rat Leydig cell. Competition of various beta-adrenergic agonists and antagonists with [3H]CGP indicates an order of potency of L-isoproterenol greater than epinephrine = salbutamol greater than norepinephrine greater than D-isoproterenol and dl-propranolol = ICI 118,551 much greater than atenolol, respectively. These observations suggest that the binding sites are predominantly of the beta 2-receptor subtype. Incubation of freshly isolated rat Leydig cells with luteinizing hormone (100 ng/ml) caused consistent stimulation of androgen production, but only occasional stimulation by the beta-agonist isoproterenol (10 microM) was observed. However, these cells consistently responded to the beta-agonist after 3 h in primary cultures. These findings indicate that rodent Leydig cells possess beta-adrenergic binding sites and point out a possible dissociation between receptor recognition and physiologic response.

Adrenergic beta-Antagonists↗
PubMed1985

Phospholipid methylation by intact rat Leydig cells.

Phospholipid methylation by intact Leydig cells was investigated by determining the incorporation of radioactivity from [3H-methyl] methionine into phospholipids. Leydig cells incorporated significantly more radioactivity into phospholipids than did unpurified testicular cells, non-Leydig testicular cells, or red blood cells. Approximately 40% of the radioactivity was found in phosphatidylcholine, indicating that the methyltransferase pathway for the synthesis of this phospholipid is highly active in rat Leydig cells. Addition of luteinizing hormone to cells preloaded with [3H-methyl] methionine did not alter the rate of phospholipid methylation. However, phospholipid methylation by Leydig cells desensitized by the injection of human chorionic gonadotropin 1 to 7 days previously was reduced by approximately 60%. Inhibition of phospholipid methylation to 75% of normal with homocysteine thiolactone did not affect luteinizing hormone-stimulated androgen production. Further inhibition of phospholipid (and protein) methylation by treatment with homocysteine thiolactone and 3-deazaadenosine significantly reduced luteinizing hormone-stimulated androgen production. The results of this study demonstrate that the methyltransferase pathway for the synthesis of phosphatidylcholine is highly active in intact Leydig cells but is reduced in desensitized Leydig cells. There does not appear to be a close association between the activity of this pathway and the ability of luteinizing hormone to acutely stimulate androgen production.

Animals↗
PubMed1984

Beta 2-adrenergic stimulation of androgen production by cultured mouse testicular interstitial cells.

The present studies characterized the beta-receptor subtype involved in androgen production by cultured mouse testicular interstitial cells and explored the possible stimulation of androgen release by alpha-adrenergic agonists. During a 3-hour incubation period, LH and a non-specific beta-adrenergic agonist, L-isoproterenol steadily increased androgen production with a similar time-course. Isoproterenol, epinephrine, norepinephrine and a specific beta 2-receptor agonist, salbutamol stimulated androgen release in a concentration-dependent manner. The concentrations of the agonists required for half-maximum stimulation (EC50) were approximately 1 nM (isoproterenol), 8 nM (epinephrine), 9 nM (salbutamol) and 2 microM (norepinephrine) giving an order of potency of isoproterenol greater than epinephrine = salbutamol much greater than norepinephrine. L- but not the D-isomer of isoproterenol induced androgen production. A non-selective beta-receptor antagonist, propranolol, abolished androgen production induced by isoproterenol. A selective beta 2-receptor antagonist ICI 118,551 inhibited the isoproterenol effect in a concentration-dependent manner with half-maximum inhibition (IC50) at approximately 23 nM. The beta 1-receptor antagonists, metoprolol and atenolol had no effect on isoproterenol-induced androgen release. The stimulatory effect of norepinephrine (an alpha- and beta-agonist) was completely (100%) abolished by propranolol, unaffected by the alpha-antagonist phentolamine and only partially (35%) inhibited by phenoxybenzamine. Phenoxybenzamine and the alpha 2-agonist, clonidine reduced basal androgen production. These studies indicate that androgen production by primary cultures of mouse testicular interstitial cells occurs exclusively via the beta 2-receptor subtype and that alpha-receptor agonists do not stimulate androgen release by these cells.

Adrenergic beta-Agonists↗