Friday 18 December 2015

Androsterone:Pheromone Resources




Androsterone


It is believed that a deficiency of androgens, including free testosterone, may promote the development of convulsions. The present study revealed differences in the action of androsterone (AND), a major excreted metabolite of testosterone and a neurosteroid, in three commonly used seizure models in mice. AND administered intraperitoneally exhibited dose-dependent protection against tonic-clonic convulsions caused by maximal electroshock (MES) with ED50 (effective dose50) of 227 mg/kg. The compound also inhibited the convulsive action of pentylenetetrazole (PTZ), increasing its CD= (convulsive dose50) for clonic convulsions from 77.2 (PTZ + saline) to 93.9 (p < 0.05) for PTZ +AND40 mg/kg and 113.9 mg/kg (p < 0.001) for PTZ +AND60 mg/kg. In mice pretreated with 60 mg/kg AND, the CD50 for PTZ-induced tonic convulsions increased from 102 to 127.6 mg/kg (p < 0.01) (Mróz, Katarzyna et al.,2009).
Intraperitoneal injection of 5 α,3α -A–protected mice in a dose-dependent fashion from seizures in the following modls (ED50, dose in mg/kg protecting 50% of animals): 6-Hz electrical stimulation (29.1), pentylenetetrazol (43.5), pilocarpine (105), 4-AP (215), and  aximal electroshock (224). 5β,3α-A also was active in the 6-Hz and pentylenetetrazol models, but was less potent (ED 50 v alues, 76.9 and 139 mg/kg, respectively), whereas epiandrosterone (5α ,3 β -A) was inactive (ED 50 , ≤ 300 mg/kg). 5 α ,3 α -A (10–100 μ M ) also inhibited epileptiform discharges in a concentration-dependent fashion in the in vitro slice model, whereas 5β ,3 α -A was active but of lower potency, and 5 α ,3 β -A was inactive (Kaminski et al.,2005).

This sexual pheromone was first discovered in 1931 by scientists in Germany. Relatively high androsterone value is associated with sexual preference for females by either sex, whereas a relatively low androsterone value is associated with sexual preference for males by either sex (James V. Kohl,2006). The effects of the androgenic hormone, androsterone sulfate, a 17-ketosteroid, on long term potentiation in the dentate gyrus (DG) of urethane anesthesized rats were reported. Intravenous injection of 10 mg of the hormone dissolved in Nutralipid produced a significant increase of the population spike (PS), but not of the excitatory post-synaptic potentials (EPSP). The results are discussed in terms of the potential enhancement that androsterone sulfate may have on memory as was described for one of its parent compounds, dehydroepiandrosterone (DHEA) and its potential use as an antidepressant  (Urbanoski et al.,2000) .
Androsterone sulfate (5α-androstan-3α-ol-17-one, 3-sodium sulfate) administered to freely moving rats via cerebroventricular cannulae induced analgesia, wet-dog shakes, body jerks, rigidity, Straub tail, hypermotility, excessive grooming, hyperreactivity to stimuli, aggression, escape behavior, EEG spiking, and behavioral and EEG seizures. These responses resemble those produced by certain opiate drugs and by beta-endorphin, an endogenous peptide; they appear during the 5-min infusion period, persist in some cases for several hours, and are diminished by pretreatment with the narcotic antagonist naloxone (LaBella et al1978).

Both  drugs favourably decreased platelet stickiness (p <000l),but the effect with clofibrate and bandrosterone (atromid) was more marked than with clofibrate alone (atromid-S). Both drugs. The effects of clofibrate with and without androsterone on platelet stickiness and the blood produced a statistically significant (p <Ol001) and similar fall in serum cholesterol; their effects on low density lipoprotein were inconstant. The changes in platelet stickiness and in the lipids appeared to be independent (Carson et al.,1966). Androsterone administered orally to 13 men with coronary heart disease in a dosage of 100 mg. daily for one month had practically no clinical or serum lipidshifting effects. In contrast, androsterone given intramuscularly to 8 men in a dosage of 50 mg. daily for one to four weeks resulted in a significant decrease in the levels of serum triglycerides and phospholipids, as well as total cholesterol, reflecting a reduction in the β-lipoprotein fraction. Despite this decrease, the frequency of local and systemic side-effects renders this compound unsuitable for routine clinical use. Androsterone was excreted in the urine chiefly as the glucuronide (Cohen et al.,1961).    


The effects of androsterone and testosterone propionate on atheroma and plasma lipid shifts induced by cholesterol feeding in cockerels were compared. Both compounds produced significant inhibition of coronary arterial atheroma. Aortic atherogenesis was not affected. The effects on plasma lipids were similar; non-significant reduction in cholesterol (C), significant decrease in phospholipid (P) with elevated C/P ratios (Cook,1960). The preputial glands of the hypophysectomized rat grow in response to steroids possessing the same molecular features which evoke growth in the prostate. Unlike the prostatic glands of the female rat, the preputial glands are constantly present. These giant sebaceous glands are useful indicators in the biological assay in the female rat of steroids with androgenic activity. There are important synergistic relationships between steroids and pituitary proteins in the promotion of growth so that hypophysectomy is necessary for the precise characterization of growth as induced by steroids ( Huggins et al.,1955).


Studied the modifying effects on the hypoplasia of organs of three hormones—thyroid, androsterone, and estradiol—given alone or simultaneously. The evidence indicates that the hypoplasia can be prevented, at least for a certain period of time, by administration of one or more of these hormones, thyroid and estradiol being particularly effective (Korenchevsky  and  Jones, 1946).


With oestradiol dipropionate  alone, the vagina  was restored to normal or supernormal weight, with normal (usually " oestrus ") structure, but not even a weekly dose of 0*2 mg. was able to produce normal size   and weight    of the uterus, although this dose caused pronounced pathological changes in the structure of this organ. 3. The weak effects of androsterone and transdehydroandrosterone on the uterus were not significantly increased, as compared within experiments of shorter duration, but the vagina and especially the preputial glands were considerably hypertrophied (Korenchevsky et al.,1939). The observed results demonstrate that daily injections of 0.5 to 3 mg. of testosterone in sesame oil and of 3.0 to 5.0 mg. of androsterone in sesame oil into normal mature female rats leads to a suppression of the oestrous cycles, as expressed by the vaginal smear, during the 16-day period of injection (Browman,1937).




References:

Browman, Ludvig G.1937.Effects of androsterone and testosterone on oestrous cycle of rats. Experimental Biology and Medicine 36(2): 205-208.
Carson, P., L. McDonald, S. Pickard, T. Pilkington, B. Davies, and F. Love.1966. Effects of clofibrate with androsterone (atromid) and without androsterone (atromid-S) on blood platelets and lipids in ischaemic heart disease." British heart journal, 28(3): 400.
Cohen, William D., Norio Higano, Roger W. Robinson, and Raoul J. Le Beau.1961. Changes In Serum Lipids And Urinary Ketosteroids During Oral And Intramuscular Administration Of Androsterone.  The Journal of Clinical Endocrinology & Metabolism 21(10):1208-1217.
Cook, Donald L.1960. Effects of androsterone on atherogenesis and plasma lipids in cockerels." Experimental Biology and Medicine 105(3): 586-588.
Huggins, Charles, Frank M. Parsons, and Elwood V. Jensen.1955. "Promotion Of Growth Of Preputial Glands By Steroids And The Pituitary Growth Hormone,  Endocrinology 57(1):25-32.
James V. Kohl. 2006.The Mind's Eyes: Human Pheromones, Neuroscience, and Male Sexual Preferences.Journal of Psychology and Human Sexuality., 18;4:313-369.
Kaminski, Rafal M., Herbert Marini, WonJoo Kim, and Michael A. Rogawski.2005. Anticonvulsant activity of androsterone and etiocholanolone." Epilepsia 46(6): 819-827.
Korenchevsky, V., and Vera E. Jones.1946. The Effects of Androsterone, Oestradiol and Thyroid Hormone on the Artificial Premature “Climacteric” of Pure Gonadal Origin Produced by Ovariectomy in Rats I. Effects on Weights of Organs. Journal of gerontology, 1(3 Part 1): 319-335.
Korenchevsky, V., K. Hall, and R. Burbank. 1939."The manifold effects of prolonged administration of sex hormones to female rats." Biochemical Journal,33(3): 372.
LaBella, Frank, Viktor Havlicek, Carl Pinsky, and Leonid Leybin.1978.Opiate-like, naloxone-reversible effects of androsterone sulfate in rats. Canadian journal of physiology and pharmacology 56(6): 940-944.
Moore, Carl R., and Price Dorothy.1937.Some Effects Of Synthetically Prepared Male Hormone (Androsterone) in the Rat.  Endocrinology 21(3): 313-329.
Mróz, Katarzyna, Tomasz Mróz, Marian Wielosz, and Piotr Tutka.2009.Effects of androsterone on convulsions in various seizure models in mice." Pharmacological Reports 61(3): 564-569.
Urbanoski, Karen, John Harris, Karel Gijsbers, and Bernardo Dubrovsky.2000. Androsterone sulfate increases dentate gyrus population spike amplitude following tetanic stimulation. Physiology & behavior 71(5): 435-440.