BIOLOGICAL ACTION OF 17?-HYDROXYPROGESTERONE 17-n-CAPROATE ON THE REPRODUCTIVE PROCESSES OF THE RAT

ABSTRACT In an attempt to find suitable animal models to aid in the study of the reproductive processes of the human male, plasma levels of unconjugated pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, 20α-dihydroprogesterone, 17-hydroxyprogesterone, androstenedione, testosterone, dihydrotestosterone, oestrone and oestradiol were measured in 18 male baboons and 10 male rhesus monkeys and the steroid levels were compared with those previously established in normospermic, middle-aged men. Significant species differences were found with regard to the three Δ5-steroids studied; whereas the approximate relationship of pregnenolone to 17-hydroxypregnenolone and dehydroepiandrosterone was 1:2:4 in men, the corresponding relationship was 1:5:30 in rhesus monkeys and 1:10:10 in baboons. Similar levels of 20α-dihydroprogesterone were found in the three species. On the other hand, the 17-hydroxyprogesterone levels in baboons were much lower and the levels of androstenedione lower than those found in men and in rhesus monkeys. No species difference was found with regard to circulating testosterone levels. However, both rhesus monkeys and baboons exhibited much higher levels of dihydrostestosterone than did men. Oestrone levels were higher in baboons than in men and oestradiol levels were higher in rhesus monkeys than in men and in baboons. The significant differences in circulating steroid levels suggest that further studies (including i.a. steroid analyses in testicular tissue, seminal plasma and spermatic artery and vein following both stimulation and suppression of testicular endocrine function) are required before preference can be given to any of the two species studied as a suitable animal model for the study of new fertility regulating agents.

Download Full-text

Abstract #810984: Discordant Serum 17-Hydroxyprogesterone and Androstenedione in the Management of Congenital Adrenal Hyperplasia: Are 11-Oxygenated-Androgens Useful?

Endocrine Practice ◽

10.1016/s1530-891x(20)39842-6 ◽

2020 ◽

Vol 26 ◽

pp. 39-40

Author(s):

Smita Jha

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Adrenal Hyperplasia ◽

17 Hydroxyprogesterone

Download Full-text

SPECIAL PROBLEMS IN TOXICITY TESTING OF LONG ACTING DEPOT CONTRACEPTIVES

Acta Endocrinologica ◽

10.1530/acta.0.075s315 ◽

1974 ◽

Vol 77 (1_Suppla) ◽

pp. S315-S354 ◽

Cited By ~ 4

Author(s):

F. Neumann ◽

R. von Berswordt-Wallrabe ◽

W. Elger ◽

K.-J. Gräf ◽

S. H. Hasan ◽

...

Keyword(s):

Biological Effects ◽

Histological Finding ◽

Toxicity Testing ◽

Prolactin Secretion ◽

List Type ◽

Human Species ◽

Prolactin Plasma Level ◽

Human Use ◽

Long Acting ◽

Reproductive Processes

ABSTRACT Two types of so-called "depot contraceptives", long-acting steroids which are of interest for human use, were studied in animals. Norethisterone oenanthate, mainly gestagenic in the human and other species, turned out to be predominantly oestrogenic in rats. This oestrogenicity caused indirectly, via an enhanced hypophysial prolactin secretion, the well-known hypophysial and mammary tumours in rats. Another synthetic gestagen, 4,6-dichloro- 17- acetoxy- 16α-methyl-4,6-pregnadiene-3,20-dione, which might be considered in its biological actions similar to preparations containing chlormadinone acetate or medroxy-progesterone acetate, induced no signs of oestrogenicity in dogs. It is surmised that its gestagenic influence indirectly, and probaby, via an enhanced hypophysial prolactin secretion caused "mammary nodules" in this "non-rodent" species. These studies have born out mainly two facts: A synthetic steroid, norethisterone oenanthate, exerted different biological effects in different species: it was a gestagen in the rabbit, whereas in rats, its predominant influence was oestrogenic. The hypophysial prolactin secretion was enhanced in various species by different mechanisms: in rats, the oestrogenicity caused an increased prolactin plasma level, whereas in dogs, a gestagen with obviously no inherent oestrogenicity, 4,6-dichloro-17-acetoxy-16α-methyl-4,6-pregnadiene-3,20-dione, converted the histological appearance of the anterior pituitary into a condition with a greatly increased number of eosinophils. This histological finding was interpreted as an indicator for a hypersecretion of prolactin. Hence, animal work with "gestagens" has only limited predictive value with respect to their possible effects in the human species. Therefore, inflexible recommendations are not helpful in solving the safety problem of long-acting steroids which affect primarily reproductive processes.

Download Full-text

EFFECT OF STRESS ON THE PROFILE OF PLASMA STEROIDS IN BABOONS (PAPIO HAMADRYAS)

Acta Endocrinologica ◽

10.1530/acta.0.0900372 ◽

1979 ◽

Vol 90 (2) ◽

pp. 372-384 ◽

Cited By ~ 20

Author(s):

N. P. Goncharov ◽

A. G. Taranov ◽

A. V. Antonichev ◽

V. M. Gorlushkin ◽

T. Aso ◽

...

Keyword(s):

Luteal Phase ◽

Immobilization Stress ◽

Marked Decrease ◽

Follicular Phase ◽

Papio Hamadryas ◽

Pronounced Increase ◽

Consistent Finding ◽

Plasma Steroids ◽

Competitive Protein Binding ◽

17 Hydroxyprogesterone

ABSTRACT Adult baboons (5 males and 5 females) were exposed to immobilization stress by being strapped to a table in a horizontal position for 2 h. In females the experiment was performed during both the follicular and luteal phase. Peripheral blood was withdrawn at frequent intervals, the first sample just before immobilization, and the last one 3 days later. A number of steroids were measured in blood plasma samples by radioimmunoassay (17-hydroxypregnenolone, 17-hydroxyprogesterone, pregnenolone, testosterone, dihydrotestosterone, progesterone, 20α-dihydroprogesterone, oestrone, oestradiol) or competitive protein binding (cortisol) techniques. The cortisol levels exhibited a marked increase in both sexes. This increase was observed already during the immobilization and lasted for approximately 24 h. A similar, even more pronounced increase was seen in 17-hydroxypregnenolone, 17-hydroxyprogesterone and pregnenolone levels. A marked, long-lasting (72 h) decrease of testosterone and dihydrotestosterone levels was a consistent finding in male baboons. This was not observed in the females which, on the other hand, exhibited a marked decrease (duration 48 h) of progesterone and 20α-dihydroprogesterone levels during the luteal phase, and a significant decrease (duration > 24 h) of oestradiol and oestrone concentrations during the follicular phase. It is concluded that stress has a marked inhibitory action on gonadal function both in male and female baboons. In females the inhibition of steroidogenetic function is exerted both on the ovarian follicles and on the corpus luteum.

Download Full-text

Inhibition of TMEM16A impedes embryo implantation and decidualization in mice

Reproduction ◽

10.1530/rep-18-0197 ◽

2018 ◽

Cited By ~ 2

Author(s):

Qianrong Qi ◽

Yifan Yang ◽

Kailin Wu ◽

Qingzhen Xie

Keyword(s):

Progesterone Receptor ◽

Stromal Cells ◽

Embryo Implantation ◽

Mouse Uterus ◽

Endometrial Stromal Cells ◽

Uterine Endometrium ◽

Molecule Inhibitor ◽

Pathway Inhibition ◽

And Function ◽

Reproductive Processes

Recent studies revealed that TMEM16A is involved in several reproductive processes, including ovarian estrogen secretion and ovulation, sperm motility and acrosome reaction, fertilization, and myometrium contraction. However, little is known about the expression and function of TMEM16A in embryo implantation and decidualization. In this study, we focused on the expression and regulation of TMEM16A in mouse uterus during early pregnancy. We found that TMEM16A is up-regulated in uterine endometrium in response to embryo implantation and decidualization. Progesterone treatment could induce TMEM16A expression in endometrial stromal cells through progesterone receptor/c-Myc pathway, which is blocked by progesterone receptor antagonist or the inhibitor of c-Myc signaling pathway. Inhibition of TMEM16A by small molecule inhibitor (T16Ainh-A01) resulted in impaired embryo implantation and decidualization in mice. Treatment with either specific siRNA of Tmem16a or T16Ainh-A01 inhibited the decidualization and proliferation of mouse endometrial stromal cells. In conclusion, our results revealed that TMEM16A is involved in embryo implantation and decidualization in mice, compromised function of TMEM16A may lead to impaired embryo implantation and decidualization.

Download Full-text

Fungicidal and Bactericidal Activity of the Alkyl-Substituted Guanidine-Containing Oligomers

Mikrobiolohichnyi Zhurnal ◽

10.15407/microbiolj82.06.054 ◽

2020 ◽

Vol 82 (6) ◽

pp. 54-63

Author(s):

M.Ya. Vortman ◽

◽

Yu.B. Pysmenna ◽

A.I. Chuenko ◽

D.R. Abdulina ◽

...

Keyword(s):

Heterotrophic Bacteria ◽

Trichoderma Viride ◽

Rhodococcus Erythropolis ◽

Biological Action ◽

Molar Ratio ◽

Diffusion Method ◽

Klebsiella Pneumonia ◽

Alkyl Bromides ◽

Base Form ◽

Two Stages

Biocides are widely used in medicine and various industries to protect against a number of harmful microorganisms. Organic quaternary ammonium and guanidine-containing compounds, the biological action of which is based on membrane-toxic properties, are used as bactericidal preparations. The aim of this work was to study the bactericidal and fungicidal activities of the synthesized oligomeric alkylsubstituted guanidinium bromides with different radicals -C3H7, -C7H15, -C10H21, against different isolates of heterotrophic bacteria and microscopic fungi. Methods. The synthesis of alkyl-substituted guanidiniumcontaining oligomers was performed in two stages. In the first stage, alkyl-substituted guanidine was obtained by the reaction of guanidine, previously converted by alkali from the salt form to the base form by the base and alkyl bromides (Alk=-C3H7 (propyl), -C7H15 (heptyl), -C10H21 (decyl)) in methanol at a temperature of 50°C and a molar ratio of 1:1. The second carried out the reaction between aromatic oligoepoxide DER-331 and alkyl-substituted guanidine in methanol at a temperature of 50°C for 2–3 hours and a molar ratio of 1:2. Bacteria were grown on meat-peptone agar for 48 hours at a temperature of 28±2°С. Test cultures of micromycetes were cultured on agar beer wort (6°B), incubated for 14 days in a thermostat at a temperature of 28±2°C. Antimicrobial activity of newly synthesized alkyl-substituted guanidinium-containing oligomers was determined by standard disco-diffusion method (method of disks on agar) and fungicidal activity was determined by the method of holes in agar. Results. Oligomeric alkylsubstituted guanidinium bromides with different radicals composed -C3H7, -C7H15, -C10H21- synthesized by the reaction of guanidine alkyl bromides with aromatic oligoepoxydes. It was found that alkyl-substituted guanidinium-containing oligomers at a concentration of 1–3% inhibited the growth of Escherichia coli 475, Pseudomonas aeruginosa 465, Klebsiella pneumonia 479, Pseudomonas pseudoalcaligenes 109, Staphylococcus aureus 451, E. faecalis 422, Rhodococcus erythropolis 102, Bacillus subtilis 138 and most of the studied micromycetes – Aureobasidium pullulans F-41430, Paecilomyces variotii F-41432, Penicillium funiculosum F-41435, Penicillium ochrochloron F-41431, Scopulariopsis brevicaulis F-41434, Trichoderma viride F-41437, Candida albicans F-41441, Aspergillus flavus F-41442, Aspergillus niger F-41448, Penicillium sp. F-41447. Conclusions. Antimicrobial and fungicidal properties significantly depend on the length of the alkyl radical, with increasing of its length the diameter of the zone of bacterial and micromycetes growth retardation increases.10.15407/microbiolj82.06.054

Download Full-text

Pharmacognostical and pharmacological activity of Justicia gendarussa burm.f.: a comprehensive review

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i3.2475 ◽

2020 ◽

Vol 11 (3) ◽

pp. 3384-3390

Author(s):

Ashish ◽

Anjali ◽

Dixit Praveen K ◽

Nagarajan K ◽

Sahoo Jagannath

Keyword(s):

Pharmacological Activity ◽

Chemical Constituents ◽

Biological Action ◽

Andaman Islands ◽

Comprehensive Review ◽

Medicinal Value ◽

Anti Oxidant ◽

Phytochemical Constituents ◽

Pharmacologically Active ◽

Different Parts

Justicia gendarussa Burm .f. (family Acanthaceae) which is also known as willow-leaves and commonly known as Nili-Nirgundi, it is very commonly found nearby to China and its availability is very common in larger parts of India and Andaman islands. Traditionally it is used to treat various sorts of disorders such as wound healing, anti-inflammatory, anti-oxidant, antiproliferative, anti-arthritic etc. Justicia gendarussa is one of the crucial herbs which has been used in the Ayurveda. Majorly leaves parts of the plant shows the pharmacological activity but the root of the plant Justicia gendarussa is also have the important medicinal values. A large variety of pharmacologically active constituents i.e., alkaloids, flavonoids, saponin, carbohydrates, steroids, triterpenoids, carotenoids, aminoacids, tannins, phenolics, coumarines and anthaquinones are also present in this plant and they makes the plant pharmacologically important. The activity of the plant is also dependent on the solvent which is used for the extraction the various vital chemical constituents. The different- different parts of the plants having the different medicinal values also differ in the chemical values. This review is not only focused on the essential phytochemical constituents which is available in the plant but it also explains their necessary medicinal value to shows the essential biological action and phytopharmacological actions of various parts of the plant.

Download Full-text

Turning Fear of Boron Toxicity into Boron-containing Drug Design

Current Medicinal Chemistry ◽

10.2174/0929867326666190327154954 ◽

2019 ◽

Vol 26 (26) ◽

pp. 5005-5018 ◽

Cited By ~ 1

Author(s):

Marvin A. Soriano-Ursúa ◽

Eunice D. Farfán-García ◽

Simonetta Geninatti-Crich

Keyword(s):

Drug Design ◽

Qualitative Content Analysis ◽

Biological Action ◽

Research Literature ◽

Bibliographic Databases ◽

Boron Toxicity ◽

Withdrawal Period ◽

Analysis Methodology ◽

Structure Activity ◽

Toxicological Data

Background: Despite the historical employment of boron-containing compounds (BCCs) with medicinal purposes, the reported cases of BCC toxicity in humans during the twentieth-century drived us towards a “boron-withdrawal” period. Fortunately, the use of boric acid for specific purposes remains, and the discovery of natural BCCs with biological action attractive for therapeutic purposes as well as the introduction of some new BCCs for clinical use has reactivated the interest in studying the properties of these BCCs. Methods: We carried out a structured search of bibliographic databases for scientific peerreviewed research literature regarding boron toxicity and linked that information to that of BCCs in drug design and development. A deductive qualitative content analysis methodology was applied to analyse the interventions and findings of the included studies using a theoretical outline. Results: This review recapitulates the following on a timeline: the boron uses in medicine, the data known about the toxicological profiles of some BCCs, the pharmacological properties of some BCCs that are employed in cancer and infectious disease therapies, and the known properties of BCCs recently introduced into clinical assays as well as the identification of their structure-activity relationships for toxicity and therapeutic use. Then, we discuss the use of new approaches taking advantage of some toxicological data to identify potent and efficient BCCs for prevention and therapy while limiting their toxic effects. Conclusion: Data for boron toxicity can be strategically used for boron-containing drug design.

Download Full-text