John Steinbeck Jackson J Benson Susan Sh Popular Books
John Steinbeck Jackson J Benson Susan Sh Biography & Facts
The pharmacology of progesterone, a progestogen medication and naturally occurring steroid hormone, concerns its pharmacodynamics, pharmacokinetics, and various routes of administration. Progesterone is a naturally occurring and bioidentical progestogen, or an agonist of the progesterone receptor, the biological target of progestogens like endogenous progesterone. Progesterone also has antimineralocorticoid and inhibitory neurosteroid activity, whereas it appears to have little or no glucocorticoid or antiandrogenic activity and has no androgenic activity. Because of its progestogenic activity, progesterone has functional antiestrogenic effects in certain tissues such as the uterus, cervix, and vagina. In addition, progesterone has antigonadotropic effects due to its progestogenic activity and can inhibit fertility and suppress sex hormone production. Progesterone differs from progestins (synthetic progestogens) like medroxyprogesterone acetate and norethisterone, with implications for pharmacodynamics and pharmacokinetics as well as efficacy, tolerability, and safety. Progesterone can be taken by mouth, in through the vagina, and by injection into muscle or fat, among other routes. A progesterone vaginal ring and progesterone intrauterine device are also available as pharmaceutical products. Mechanism of action Progesterone is a progestogen, or an agonist of the nuclear progesterone receptors (PRs), the PR-A, PR-B, and PR-C. In one study, progesterone showed EC50Tooltip half-maximal effective concentration values of 7.7 nM for the human PR-A and 8.0 nM for the human PR-B. In addition to the PRs, progesterone is an agonist of the membrane progesterone receptors (mPRs), including the mPRα, mPRβ, mPRγ, mPRδ, and mPRϵ. It is also a potent antimineralocorticoid (antagonist of the mineralocorticoid receptor (MR)), as well as a very weak glucocorticoid (agonist of the glucocorticoid receptor). Progesterone does not interact significantly with the androgen receptor (AR) or with the estrogen receptor (ER). In addition to its activity as a steroid hormone, progesterone is a neurosteroid. Specifically, it is an antagonist of the sigma σ1 receptor, a negative allosteric modulator of nicotinic acetylcholine receptors, and, via its active metabolites allopregnanolone and pregnanolone, a potent positive allosteric modulator of the GABAA receptor, the major signaling receptor of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Antimineralocorticoid activity Progesterone is a potent antimineralocorticoid. It has 1000% of the affinity of aldosterone, the major endogenous agonist, for the human MR, and 100% of the affinity of aldosterone for the rat MR. Progesterone produces antimineralocorticoid effects such as natriuresis (excretion of sodium in the urine) at normal physiological concentrations. A 200 mg dose of oral progesterone is considered to be approximately equivalent in antimineralocorticoid effect to a 25 to 50 mg dose of the potent antimineralocorticoid spironolactone, which itself is a derivative of progesterone. Doses of progesterone of 50 to 200 mg by intramuscular injection, which are similar to progesterone exposure in the third trimester of pregnancy, have also been reported to produce antimineralocorticoid-like effects. The antimineralocorticoid effects of progesterone underlie its ability to lower blood pressure and reduce water and salt retention and its potential application in the treatment of hypertension. An active metabolite of progesterone, 11-deoxycorticosterone (21-hydroxyprogesterone), is a precursor of aldosterone and has strong mineralocorticoid activity (i.e., is a strong agonist of the MR). However, it is formed in relatively small amounts, and any such effects produced by it are usually outweighed by the antimineralocorticoid activity of progesterone. Progesterone may be a relatively weak antimineralocorticoid in vivo. Glucocorticoid activity Progesterone is a partial agonist of the glucocorticoid receptor (GR). It has about 35% of the affinity of dexamethasone, a corticosteroid, for the human GR, and about 3 to 11% of the affinity of dexamethasone for the rat GR. However, progesterone appears to show weak or no glucocorticoid activity and no antiglucocorticoid activity in vitro and in animals. Nonetheless, progesterone has been found to upregulate the thrombin receptor in vascular smooth muscle cells in vitro, a glucocorticoid effect, and this could have clinical relevance in relation to risk of blood clots. Androgenic and antiandrogenic activity The binding and activity of progesterone at the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT) in the body, is controversial. Some studies have found progesterone to bind to the AR, with agonistic and antagonistic activity exerted, whereas other studies have found very low or no affinity for the AR at all. In animal studies, no androgenic effects have been observed, but weak antiandrogenic effects have been reported. The weak antiandrogenic activity has been attributed not to antagonism of the AR by progesterone, but rather to its weak 5α-reductase inhibition and consequent inhibition of the conversion of testosterone into the more potent DHT. There is no clinical evidence of AR-mediated androgenic or antiandrogenic activity with progesterone. Progesterone has not been associated with any classical androgenic effects in clinical studies in women, including no changes in the blood lipid profile or sex hormone-binding globulin levels, acne, oily skin, hirsutism, or voice deepening, nor with virilization of female fetuses. As such, the scientific consensus is that progesterone is clinically neither androgenic nor antiandrogenic. This is in contrast to many progestins, such as 19-nortestosterone derivatives (e.g., norethisterone, levonorgestrel, dienogest) and 17α-hydroxyprogesterone derivatives (e.g., cyproterone acetate, medroxyprogesterone acetate), which do bind to the AR and have been associated with significant androgenic or antiandrogenic effects depending on the progestin in question. Due to its lack of androgenic and antiandrogenic activity, and hence lack of masculinizing and feminizing effects, progesterone is one of the few progestogens that is suitable for use during pregnancy in women at risk for preterm birth or recurrent miscarriage. Although progesterone does not have significant AR-mediated androgenic or antiandrogenic activity, it is a precursor and intermediate, albeit distant, in the biosynthesis of androgens from cholesterol. For this reason, there has been some speculation that exogenous progesterone could be transformed into androgens by certain tissues that express the requisite enzymes. Progesterone is converted by 17α-hydroxylase into 17α-hydroxyprogesterone; 17α-hydroxyprogesterone is converted by 17,20-lyase into androstenedione; and androstenedione is converted by 17β-hydroxysteroid dehydrogenases into .... Discover the John Steinbeck Jackson J Benson Susan Sh popular books. 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Best Seller John Steinbeck Jackson J Benson Susan Sh Books of 2024
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The Honeymoon Homicide
J. R. Mathis & Susan MathisEnjoy this SmallTown Murder Mystery Featuring A Unique Sleuthing Couple I'm Father Tom Greer, a Catholic Priest in a smalltown parish who never expected this . . . When I came...
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Never Enough
Lexy TimmsBe good enough never is... Anthony Accardi is a man on a mission: make his father's watch company a success while bringing in millions of dollars. To do that, he needs an assi...
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Become A Better Version of Yourself
Ben LeightonThis ebook contains golden nuggets on how to motivate, inspire and improve your current situation. It encompasses the holistic view of self improvement from mental& emotion...
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The Cupcake Cottage
Jean OramNHL player Maverick Blades could fall in love with anyone... But he had to fall for a woman who falls under the Bro Code as untouchablehis best friend’s beautiful ex, DaisyMae Ray....
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Coffee Girl
Sophie SinclairMackenzie "Kiki" Forbes finds herself in a pickle. Either become her snarky sister's nanny, or move halfway across the country to work as assistanttothestylist of a ...
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Teach Me
Cassandra DeanFrom awardwinning author Cassandra Dean comes a tale where lessons of pleasure between a curious, sunshine widow and a dissolute, grumpy earl leads to passion and allconsuming love...
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Teased by Fire
Molly O'HareFrom USA Today bestselling author Molly O’Hare comes an enemiestolovers, older brother’s best friend, romantic comedy with a curvy, antisocial, supernaturalobsessed, allyearround h...
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Christmas in Sweetbriar Cove
Melody GraceCelebrate the holidays in Sweetbriar Cove with this festive romance collection, containing two sizzling smalltown holiday stories perfect for fans of Tessa Bailey, Sophie Kinsella...
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Think and Grow Rich
Greg Habstritt & Napoleon HillThink and Grow Rich is one of the most popular success book of alltime, having sold more than 60 million copies since it was first published more than 70...
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Always Yours
Claire RayeSome things are just meant to be... Ellen Somerville and Will McIntyre met by accident and under unusual circumstances. Getting sprayed by a skunk in a parking lot wouldn’t normall...
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The Count of Monte Cristo
Alexandre DumasAn Apple Books Classic edition. Alexandre Dumas’ classic paints a portrait of Edmond Dantès, a dark and calculating man who is willing to wait years to exact his perfect plan for r...
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Law of Attraction
Jordan HollisHow to Finally Overcome the Hurdles of Manifesting Proven, effective and enjoyable ways to help you manifest faster… Right now, think of something that makes you successful. If you...
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Saltwater Cove
Amelia AddlerSecond chances...and the secrets that sabotage them. At 48 years old, Margie Clifton never expected to be starting her life all over again. But when her brother gifts her a propert...
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Becoming Lady Dalton
Carrie LomaxA dance of desire and deceit... In the glittering world of London's ton, Mrs. Viola Cartwright revels in her newfound freedom as a lady of leisureuntil a series of jewel theft...
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The Holy Bible - King James Version
King JamesHoly Bible King James Version Few Sample Paragraphs from The Holy Bible eBook, Genesis (OT) 1 Gen. 1 IN the beginning God created the heaven and the earth. 2 And the earth was with...
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You Are Kind
Michael GordonA little kindness goes a long way. How can you help encourage your kids to be kind from a young age? Teach kindness to preschoolers Acts of kindness can be fun, easy, and make a ...
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Just Me
Lexy TimmsWe all need somewhere where we feel safe… After leaving her abusive husband, Katherine Marshall is out on her own for the first time. She's hopped from city to city to avoid t...
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The Icing on the Cake
Linda SeedShe’s a baker without a kitchen. He’s got a double oven to spare. It’s a recipe for success, until his mother starts stirring up trouble … Cassie Jordan has a sweet dream to open a...
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Once Upon A One-Night Stand
Zoey LockeAt first sight, there was electrifying chemistry.  So why not go for it? After all, Lynx Grove, the city's most eligible bachelor, wants to claim her, at least for th...
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Death at Hazel House
Betty Rowlands‘Riveting, can't put it down! I love this story… a wonderfully twisted tale of a crime that has more twists than I thought possible... fantastic.’ Goodreads Reviewer, 5 stars ...
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The Adventures of Sherlock Holmes
Arthur Conan DoyleAn Apple Books Classic You get not one, not two, but 25 gripping mysteries in Arthur Conan Doyle’s first of five collections of Sherlock Holmes short stories. Follow the brilliant ...
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Bewitching a Highlander
Roma CordonDefying all for the love of a bewitching lass. Breena MacRae, a healer from Skye with a touch of witchery in her blood, embarks on a dangerous search for her missing father. She ar...
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A Green Kind of Witch
Sierra CrossCinderella crossed with Mean Girls.   That's what Hazel's daily existence feels like. Born to a family of elegant yet shallow Beige Witches, seventeen y...
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School of Potential
W.J. MayUSA Today Bestselling author, W.J. May brings you a continuation of the international bestselling series, The Chronicles of Kerrigan! Come back and enjoy the famous characters, or ...
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Hard Love
Peyton BanksHe was football royalty. Legendary quarterback. A champion.  Reiner Strickland had led his team to three national championships and playing a knight in shining armor was a...
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The Odyssey
HomerAn Apple Books Classic edition. Homer’s eighthcentury epic poem is a companion to The Iliad . It tells the story of Odysseus, who journeys by ship for 10 years after the Trojan War...
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Pride and Prejudice
Jane AustenAn Apple Books Classic edition. Jane Austen’s beloved classic opens with this witty and very memorable line: “It is a truth universally acknowledged, that a single man in possessio...
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All Fired Up
Kathryn ShayCaptain Jarek Zenko, a war veteran and firefighter, meets Lacey Roth at a bar one night. They don’t share their real identities, even when they retreat to a hotel. When they meet t...
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The Three Little Pigs
Mark LeskyClassic fairy tales, legends and folk stories in short version without violence retold with lovely illustrations in simple language. Perfect for reading aloud to small chi...
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The Seduction Series Boxset
Roxy Sloane“Sensual, thrilling and wild!”   Discover the bestselling series in one collection: THE SEDUCTION, THE BARGAIN, and THE INVITATION. Perfect for fans of Ana Huang, Sierra S...
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Alpha
Sybil BartelBillionaire. Mercenary. Navy SEAL. The Teams trained me to be a killer. War taught me to be ruthless. Then an illfated mission proved I was human. Combat wounded, cut loose by the ...
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The Wonderful Wizard of Oz
L. Frank BaumAn Apple Books Classic edition. You’ve seen the iconic 1939 movie, but do you know about the talking field mice, the Winkies, and the Witch of the North that appear in the original...
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Tempting the King
Jessa YorkAn escaped Mafia Queen, hiding from her past. A Mafia King who wants to claim her… Giselle They think I'm lostbut I know better. I can never be found. The path I've creat...
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A Christmas Carol
Charles DickensAn Apple Books Classic edition. It’s Christmas Eve in Victorian England. While some families don’t know where their next meal will come from, Ebenezer Scrooge sits in his large hom...
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Little Women
Louisa May AlcottAn Apple Books Classic edition. Meet the Marches! Louisa May Alcott’s classic introduces us to four unforgettable sisters: beautiful Meg, tomboyish Jo, delicate Beth, and Amy, the ...
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My Paper Heart
Magan VernonOne piece of paper can change everything After my parents received the letter I failed out of college, they didn't ask questions. They just sent me to work for my great aunt i...
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Hot Off the Press
Lexy Timms"This is what really happened… reported by a free press, for a free people…" Wes Shaw leads a secret double life. As the secret owner of a billion dollar newspap...
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Wuthering Heights
Emily BrontëAn Apple Books Classic edition. If you’ve only ever seen Wuthering Heights on screen, you may have an image of Catherine and Heathcliff as the ultimate starcrossed lovers. But that...
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Awaken Me
Jenna JacobHe was more than a ghost haunting my dreams…he was real. By day, I’m Julianna Garrett …a prim, proper accountant. By night, I’m tormented by dreams of an alpha, ambereyed Adonis wh...
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Caught Up with the Captain
Kait NolanCan a retired naval commander and the love he left behind overcome a 34yearold secret to find their way to a second chance? Captain Mitchell Greyson is a man who believes in duty. ...
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The Art of War
Sun TzuAn Apple Books Classic edition. It’s believed that Sun Tzu wrote this Chinese military primer during the 5th century BChundreds of years before the Bible. The book’s 13 chapters ex...
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Peace on Earth
Maia RossCrime never takes a holiday. Why should Irma? Irma Abercrombie is an energetic retiree with a shadowy past, a mean right hook, and a profound love of Christmas. Surrounded by seaso...
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The Stoic Mind
Addy Osmani & GoLimitlesssDiscover the timeless wisdom of Stoicism in a modern context with "The Stoic Mind," an enlightening visual guide by Addy Osmani and GoLimitlesss. This rich exploration co...
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Rogue Alpha
Kimber WhiteOne touch made her crave him. But the pull of fate could be the path to ruin. College student Laura Prince lands a plum internship deep in the Michigan wilderness. When she discove...
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The Next Girl
Carla KovachIF YOU ONLY READ ONE BOOK THIS YEAR, MAKE IT THE NEXT GIRL... You thought he’d come to save you. You were wrong. ‘ Absolutely the best thriller I’ve read this year! ’ Goodreads Rev...
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Man In The Water
Jon HillAn attempted murder. A missing spouse. And an international conspiracy that could change the world. Jack Green has always been skeptical of socalled facts. Though he's forced ...
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The Scarlet Letter
Nathaniel HawthorneAn Apple Books Classic edition. Hester Prynne lives in infamy. After committing adultery and bearing a child with a man whose name she refuses to divulge, the heroine of Nathaniel ...
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His Girl Next Door
Khardine GrayFrom USA Today Bestselling author Khardine Gray comes a sizzling hot single dad romance you won't want to miss. No strings attached fun with the ubergorgeous single d...
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Good Guy
Kate MeaderHe's a Special Forces veteran making his pro hockey debut. She's a dogged sports reporter determined to get a scoop. She's also his best friend's widow . . . Fa...
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Escape, A New Life
David J AntocciTo save herself, she had to lose everything. Trapped in a tropical paradise with no memory of how she got there, Abby is thrust into a fight for her life. Hunted by a madman, and c...