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Steroid-based Drugs

Steroid-based Drugs. Adrenocortical Hormones. Adrenocortical Hormones. Adrenal gland : Medulla : produces Epinephrine (stimulated by sympathetic impulse) Cortex : Zona glomerulosa – produces Aldosterone (stimulated by Angiotensin II and ACTH)

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Steroid-based Drugs

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  1. Steroid-based Drugs • Adrenocortical Hormones

  2. Adrenocortical Hormones Adrenal gland: • Medulla: • produces Epinephrine(stimulated by sympathetic impulse) • Cortex: • Zona glomerulosa – produces Aldosterone(stimulated by Angiotensin II and ACTH) • Zona fasciculata – produces Glucocorticoids(stimulated by ACTH = Corticotropin) • Zona reticularis – produces Androgens(physiological role unclear)

  3. Adrenocortical Hormones Steroid hormone synthesis: • Pregnenolone synthesis is rate-limiting step • C21 hydroxylase: • Prevents hydroxylation of C17 (-> c) => Only mineralocorticoids • C17 hydroxylase: • Hydroxylation of C17 (-> f, g) can be followed by hydroxylation of C11 and C21 (-> h, j, k) => Sex hormones and glucocorticoids • P450C17a hydroxylase: • Produces 17-Keto-steroids (-> l) => Sex hormones

  4. Adrenocortical Hormones Steroid hormone classification: • Progesterone: • C21 • C 3: =O • C17: -OH or =O • Mineralocorticoids: • C21 • C21: -OH • C3: =O • Glucocorticoids : • C21 • C21, C17: -OH • C 3: =O • C11: -OH or =O • Estrogens : • C18 • C17: -OH or =O • C 3: -OH • Androgens : • C19 • C17: -OH • C 3: =O

  5. Adrenocortical Hormones Glucocorticoids (GC): • 抑制所有型態的發炎反應 • 促進胎兒肺部發育（Promote fetal development (lungs) ） • 抑制 NFkB nuclear translocation => transcription of proinflammatory mediators is prevented • Lipocortin 向上調節 => 抑制 PLA2 => 不會有 PG 以及 LT 之合成 • 增加的GC 所帶來的不良效應: • 免疫被壓抑（）Immune suppression • 葡萄糖釋放增加 (=>亦即有名的類固醇型糖尿病 “steroid diabetes”) • 葡萄糖將會轉變為脂肪=>造成肥胖 adiposity • 對於蛋白質的異化增加 => 肌肉萎縮muscle atrophy • 鹽分以及水的滯留Salt and water retention (增加的 GC 將會導致 ACTH 降低 => 因此降低了醛固酮（aldosterone）的數量) => 高血壓（hypertension） • 骨質疏鬆（Osteoporosis）

  6. NF-κB 整理 • NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) 本身係一種蛋白質複合體；該複合體扮演轉錄因子（transcription factor）。可以在所有的細胞中找到 NF-κB ，該蛋白功用牽涉到對於外界壓力之反應、 • 其項目包括（cytokines, free radicals, ultraviolet irradiation, oxidized LDL以及細菌與病毒抗原之反應） 。 • NF-κB 在對於感染過程中扮演關鍵性角色；倘若NF-κB出了問題則可能與癌症、發炎、自體免疫相關之。 • 此外 NF-κB 已被證明擁有 synaptic plasticity 以及 memory

  7. NF-κB action 之作用機轉 Mechanism of NF-κB action. In this figure, the NF-κB heterodimer between Rel and p50 proteins is used as an example. While in an inactivated state, NF-κB is located in the cytosol complexed with the inhibitory protein IκBα. Through the intermediacy of integral membrane receptors, a variety of extracellular signals can activate the enzyme IκB kinase (IKK). IKK, in turn, phosphorylates the IκBα protein, which results in ubiquitination, dissociation of IκBα from NF-κB, and eventual degradation of IκBα by the proteosome. The activated NF-κB is then translocated into the nucleus where it binds to specific sequences of DNA called response elements (RE). The DNA/NF-κB complex then recruits other proteins such a coactivators and RNA polymerase, which transcribe downstream DNA into mRNA, which, in turn, is translated into protein, which results in a change of cell function

  8. Adrenocortical Hormones Glucocorticoids (GC): • Adrenal cortex failure (= Addison’s disease) 缺乏GC 之產生： • 慢性衰竭、肌肉衰弱Chronic fatigue and muscle weakness. • 食慾喪失，體重減輕 • 低血壓（hypotension） • Blotchy, dark tanning and freckling of the skin (這是因為喪失回饋機制feedback missing =>此舉將會造成 corticotropin 濃度上升) • 血糖濃度不正常 • 對於壓力反應不良 • Adrenal cortex tumors (= Cushing Syndrome) GC overproduction • Upper body obesity • “Buffalo hump” • Red, round face • Hypertension • Water retention • Thin skin and bruising • Poor wound healing

  9. Adrenocortical Hormones Glucocorticoids (GC): Clinical uses: • Allergic Rhinitis • Rheumatoid Arthritis • Asthma • Multiple Sclerosis • Carpal Tunnel Syndrome • Dermatitis • COPD • Osteoarthritis • Gout • Psoriasis • Inflammatory Bowel Disease • Sinusitis • Lupus Erythematosus • Many conditions flare up if GC therapy is discontinued due to adreno-corticol atrophy

  10. Adrenocortical Hormones Glucocorticoids (GC): • Hydrocortison (= Cortisol) • 人體中主要的糖皮質素 • 可以與 mineralocorticoid receptor 結合之(但是記住：Cortison 卻不行) • 可以充當補充治療（針對 ddison’s Disease) • 大部分都是利用外敷（用） 這是因為該藥物的 sodium-retaining effects

  11. Addison‘s disease 細內分泌出現異常所導致。其症狀包括：體重減輕、疲勞低血壓等。其並因為：腎臟內分泌腺體並沒有生產足夠的激素如 cortisol ，有時候是所謂的醛固酮（aldosterone），這些問題我們統稱為 adrenal insufficiency, or hypocortisolism. • Cortisol ：有數百種生理效應；但最重要的是：協助身體對於壓力做出適當的反應 ，其效應整理如下： • 幫助人體維持血壓、以及心血管功能 • 幫助延緩對於免疫系統的反應時間 • 協助平衡胰島素所帶來的效果（對於醣類分子之降解） • 幫助調控蛋白質、醣類以及脂肪的代謝的調控 • 幫助維持幸福感覺（helps maintain proper arousal and sense of well-being）

  12. 糖皮質素整理 • 糖皮質素（“glucocorticoid” ）：顧名思義係衍生於該類固醇與葡萄糖代謝有關。在飢餓狀態（fastedstate）中，cortisol將會刺激數種反應，而這些反應皆可以增加用來維持血糖的濃度   • 代謝效應（Metabolic effects）： • 刺激糖質新生作用（gluconeogenesis），特別是在肝臟中（注意：糖質新生作用係利用非六碳糖做為原料例如胺基酸、以及甘油此反應對於食肉動物、草食動物都是很重要的反應），該激素將會刺激糖質新生作用中相關酵素的表現 • 促進從非肝臟組織中胺基酸的運輸；此舉可以對糖質新生作用產生出正面的幫助。 • I抑制脂肪細胞以及肌肉細胞對於葡萄糖的攝取；此舉可以幫助提升血糖值 • 刺激脂肪組織中脂肪降解，藉由酯解作用，可以讓肌肉細胞可以利用酯解作用所產生出脂肪酸（當然將脂肪酸充當能量來源；至於甘油則一如前述可以充當糖質新生作用的受質）

  13. Prednisone Prednisolone Adrenocortical Hormones Glucocorticoids (GC): • Prednisone • Inactive until converted to • Prednisolone • Drug of choice for systemic application • Lower sodium-retaining effects

  14. Adrenocortical Hormones Glucocorticoids (GC): • Triamcinoline • Stronger anti-inflammatory (5x) than cortisol • No sodium-retaining effect HalogenatedGC • Betamethasone • Dexamethasone • 30x more potent than cortisol • No water and sodium retaining effects

  15. Adrenocortical Hormones Glucocorticoids (GC): • Administration • Oral • Nasal • Cutaneous • IV • Inhalation

  16. Steroid-based Drugs • Sex Steroids

  17. Sex Steroids • 女性生殖週期（Female reproductive cycle） • Gonadotropin Releasing Hormone(GnRH) = Gonadoliberin 刺激以下激素之釋放另名為： Luteinizing-hormone releasing hormone • Follicle stimulating hormone(FSH) = Follitropin • Luteinising Hormone(LH) = Lutropin 此激素可以刺激以下激素的生產 • Estrogens (E) and Gestagens (G) 此激素將可以輪流進行負控制 • Pituitary (E+G) Hypothalamus (G)激素生產

  18. GNRH as a neurohormone • GNRH as a neurohormone • GNRH is considered a neurohormone, a hormone produced in a specific neural cell and released at its neural terminal. A key area for production of GNRH is the preoptic area of the hypothalamus, that contains most of the GNRH-secreting neurons. GNRH is secreted in the hypophysial portal bloodstream at the median eminence. The portal blood carries the GNRH to the pituitary gland, which contains the gonadotrope cells, where GNRH activates its own receptor, gonadotropin-releasing hormone receptor (GNRHR), a seven transmembrane G-protein coupled receptor that stimulates the beta isoform of Phosphoinositide phospholipase C, which goes on to mobilize calcium and protein kinase C. This results in the activation of proteins involved in the synthesis and secretion of the gonadotropins, LH and FSH. GNRH is degraded by proteolysis within a few minutes.

  19. FSH 與 LH 之控制 • 在腦下垂體， GNRH 將可以刺激促性腺激素（gonadotropins,）的合成與分泌。分別為濾泡刺激激素以及黃體激素stimulates the synthesis and secretion of the follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These processes are controlled by the size and frequency of GNRH pulses, as well as by feedback from androgens and estrogens. Low frequency GNRH pulses lead to FSH release, whereas high frequency GNRH pulses stimulate LH release. • There are differences in GNRH secretion between females and males. In males, GNRH is secreted in pulses at a constant frequency, but in females the frequency of the pulses varies during the menstrual cycle and there is a large surge of GNRH just before ovulation.

  20. Sex Steroids • Female reproductive cycle • Cycle length varies from 21-35 days • Menstruation 3-6 days • First (= Proliferative) phase: • Variable (7-21 days) • FSH and LH promote follicle development • One follicle becomes the Graafian follicle(the rest degenerate) • Graaffian Follicle: • Consists of thecal and granulosa cellswhich surround the ovum • FSH-stimulated granulosa cells produce estrogens from androgen precursors generated by LH-stimulated thecal cells • Estrogens are responsible for the proliferative phase: increase in thickness and vascularity of endometrium; secretion of protein+ carbo-rich mucus • Constant low estrogen inhibits LH/FSH production BUT high estrogen cause surge of LH production => swellign and rupture of Graafian follicle = Ovulation

  21. Sex Steroids • Female reproductive cycle • Second (= Secretory) phase: • Secretory phase constant (~ 14 days) • LH-stimulated ruptured follicle developsinto Corpus luteum which secretsProgesterone • Progesterone (Pg) is responsible for the secretory phase: endometrium becomessuitable for implantation; mucus thickens • Thermogenic effects of Pg =>body temperature increase 0.5º C • Without implantation: Pg secretion stops=> menstuation is triggered • With implantation: continued Pg productionwhich (via inhibition of LH and FSH prod.) blocks further ovulation • Chorion (“precursor” of placenta) secreteshuman chorionic gonadotropin (HCG) whichmaintains endometrium lining throughoutpregnancy (HCG -> see pregnancy test)

  22. Sex Steroids • Female reproductive cycle

  23. Sex Steroids Estrogens All produced from androgen precursors Three main endogenous estrogens: • Estradiol • 人體中主要雌激素 • 有關乳癌的發展Breast development • 可以改善骨骼密度Improving bone density • 子宮發育Growth of the uterus • 加速骨骼的成熟以及骨垢閉合Accelerating bone maturation and epiphyses closure • 子宮內膜發育以支持懷孕過程的進行 • 促進陰道黏膜的厚度以及分泌 • 增加HDLIncrease HDL • Estrone • Estriol • 僅出現於懷孕過程中（由胎兒製造） (made by fetus)

  24. Sex Steroids Estrogens • Estrogens誘導助孕酮受體表現 • 助孕酮將會抑制雌激素受體（estrogen receptors）表現 • 因此同學需要記住：有兩種雌激素受體可以充當藥物作用標靶 • Estradiol • 並不能充當口服藥物（因為該藥物將會被肝臟迅速地去除(rapid hepatic elimination)） => 擁有穩定的衍生物（stable derivatives） • Ethinylestradiol • Diethyl-Stilbestrol • Stilbene derivative

  25. Sex Steroids Estrogens • Mestranol • 可以充當口服避孕藥物（ oral contraceptives） • 本身不具有活性（Inactive） => 當箭頭所指的 C3-甲氧基（methoxy group ）將會產生出 ethinylestradiol • Raloxifene • Selective estrogen receptor modifier (=SERM) • Antiestrogenic effects on breast and endometrium • Estrogenic effects on bone and lipid metabolism => use in postmenopausal osteoporosis Clinical uses of estrogens: • Replacement therapy (Turner syndrome; menopause) • Contraception • Cancer therapy

  26. Sex Steroids Anti-Estrogens • Tamoxifen • 抗雌激素效應（Antiestrogenic effects ）：在乳腺組織中出現之 • 其抗雌激素活性較弱（對於骨骼以及脂肪代謝而言） • Clomiphene • 抑制雌激素與腦下垂體結合=>如此一來將會消除所謂的回饋抑制發生=>排卵發生（ovulation） 臨床上抗雌激素（anti-estrogens）的應用 • 乳癌治療（Breast cancer therapy）(Tamoxifen) • 治療不孕症（Infertility）(Clomiphen)

  27. Sex Steroids Progesterons • 助孕酮（Progesterone） • 抑制子宮收縮Inhibits rhythmic contractions of the myometrium • 並不適合口服（Not suitable for oral administration ）(肝臟快速分解) =>以下為該化合物的穩定衍生物（stable derivatives） : • Hydroxyprogesterone • Medroxyprogesterone

  28. Sex Steroids Progesterons Testosterone derivatives with progesterone activity: • Norethindrone • Norgestrel • Desogestrel

  29. Sex Steroids Anti-Progesterons • Mifepristone (RU486) • 在1980代時發展成功（ French company Roussel Uclaf ） • 發明過程：在調查糖皮質激素受體拮抗劑（ glucocorticoid receptor antagonists ）過程中居然讓該科學家發現了與其類似的助孕酮受體拮抗劑（ blocked the similarly shaped progesterone receptor ），此舉因而促成RU486的生產 。 • 在1982年，充當墮胎工具（當然實驗室在法國進行）。僅利用一單純化合物即可誘導出完全的流產（ 80% of women up to 49 days’ gestation ） • 添加少量的前列腺素類似物（ prostaglandin analogue），將可以在數天之後刺激尿道收縮（僅需要上述步驟，其墮胎效果居然達到100%[該數據為白種人所得；注意：不是台灣人]） • 在2000在美國被批准在懷孕早期（defined as 49 days or less）進行墮胎

  30. Sex Steroids • Male reproductive system • Gonadotropin Releasing Hormone(GnRH) = Gonadoliberin stimulates release of • Follicle stimulating hormone (FSH)(Stimulates Sertoli cells => promotes gametogenesis) and • Luteinising Hormone (LH) = Interstitial Cell Stimulating Hormone (ICSH) which triggers production of • Testosterone (T) (by Leydig cells) which in turn negatively regulates • Pituitary and Hypothalamus hormone production

  31. Sex Steroids Androgens • Testosterone • 主要的雄性激素 • 擁有雄性激素以及同的發展化作用上的效應 ： Androgenic effects: • 男性雄性器官的生長以及發育 • 對於男性的 sex drive（性慾）以及 performance • 第二性徵得發育Development of secondary sexual characteristics • 對於精子生成屬重要 Anabolic effects: • 肌肉質量發育 • 可以逆轉異化反應所帶來的效應 • Dihydro-Testosterone • 活性的代謝物（Active metabolite） • 媒介重要的睪固酮作用

  32. R Sex Steroids Androgens • Testosterone • 口服之後將會被肝臟代謝殆盡 • 注射之後，其半衰期短 => ester derivatives: Proprionate, enanthate, cypionate… • Fluoxymesterone • 口服之後將會被肝臟代謝殆盡Hepatic elimination after oral administration

  33. Sex Steroids Anabolic Androgens Testosterone derivatives: anabolic effects dominant • Nandrolone • Injection • Stanozolol • oral administration

  34. Sex Steroids 同化雄性激素Anabolic Androgens • Dehydroepiandrosterone (DHEA) • 在健康食品店之中市一普遍受到歡迎的項目僅在不久之前方改為處方項目 • 實際上該化合物為睪固酮前驅物（testosterone precursor） • 如果維持DHEA之血中濃度將有助於維持記憶、活力等年輕的瘦瘦的體態（Oh!MyGod!）並中和壓力激素所帶來的負面影響 • 以下才是各位應該更要知道的：DHEA may have serious side effects: • 如果不尋常地增加睪固酮的濃度，其副作用為：青春痘（ acne ）、睪丸縮小（testicular atrophy ），罹患前列腺癌的比例大增 • 女性攝取過量的DHEA在文獻上將會有青春痘、臉上長毛髮等 • DHEA 會在體內轉變為雌激素（estrogen），因此高量的DHEA將會導致雌激素的副反應等（如女乳症），當然乳癌比例上升 • DHEA 在市場上正被行銷。這是種嚴重的誤導（misleading

  35. Sex Steroids Anti-Androgens • Flutamide • Non-steroidal receptor antagonist • 用於前列腺癌治療（prostate cancer treatment） • Finasteride • Inhibits 5a-reductase =>因此將可以預防睪固酮被轉化為dihydrotestosterone (DHT)（比睪固酮更具有效果） • 可以治療前列腺腫大、掉髮等 （因為掉髮患者體內擁有高量的DHT)

  36. Flutamide 詳細作用機轉 Flutamide is an oral antiandrogen drug primarily used to treat prostate cancer. It competes with testosterone and its powerful metabolite, dihydrotestosterone (DHT) for binding to androgen receptors in the prostate gland. By doing so, it prevents them from stimulating the prostate cancer cells to grow. Flutamide has been largely replaced by a newer member of this class, bicalutamide, due to a better side-effect profile. Flutamide may also be used to treat excess androgen levels in women. It is marketed by Schering-Plough under the brand name Eulexin. It is also known as Flutamin

  37. Sex Steroids GnRH analogs/modifiers • Danazol • Inhibits GnRH release => no FSH/LH production => no steroid production • Used to treat endometriosis (growth of endometrial tissue outside of the uterus) • Synthetic GnRH (Gonadorelin, Buserelin, Leuprorelin…) • 合成的較天然有效200X(thanGnRH) • If given in pulses (s.c.) stimulate gonadotropin release => induce ovulation • If given continously they desensitize the GnRH receptors => gonadal suppression (“medical castration”) • Used in sex hormone-dependent conditions (prostate, breast cancer; endometriosis; uterine fibroids…) • Side effects: menopausal symptoms

  38. Danazol Danazol is a derivative of the synthetic steroid ethisterone, a modified testosterone. Also known as 17alpha-ethinyl testosterone. Before becoming available as a generic drug, Danazol was marketed as Danocrine in the United States. 係用來治療子宮內膜異位（在專利藥時期；1970年代）。但該藥物有嚴重副作用：亦即讓女性產生男性副性徵（ masculinizing side-effects ）。其扮演角色即為GnRH促效劑（ GnRH agonists ）所取代。It was approved by the U.S. Food and Drug Administration (FDA) as the first drug to specifically treat endometriosis in the early 1970s.[1] Although effective for endometriosis, its use is limited by its.[2] Its role as a treatment for endometriosis has been largely replaced by the.

  39. Sex Steroids Oral Contraceptives • History • 1937: Investigators demonstrated that the female hormone progesterone could halt ovulation in rabbits • 1949: Scientists at the University of Pennsylvania achieved the production of synthetic progestins • 1953: Margaret Sanger, Katherine McCormick and Gregory Pincus team up to develop a reliable contraceptive • 1950s: Large scale testing of “the pill” was successful • 1960: FDA approves first oral contraceptive (Early pill formulations contained up to 150 micrograms (mcg) of estrogen!) • 1982/84: Introduction of the bi- and tri-stage formulation • 1988: FDA recognized several severe long-term side effects (high estrogen!) • Currently used by 16 mill. women in the US (40% of women between 18 and 24

  40. Sex Steroids Oral Contraceptives Either combination estrogen/progesterone of progesterone alone • Combination pills: • Highly effective • Estrogen component is mostly ethinylestradiol, sometimes mestranol • Progesterone component varies • 21 day cycle with 7 day break (causes withdrawal bleeding) • Can be mono- or biphasic Mechanism: • Estrogen inhibits FSH secretion (neg. feedback loop!) => suppression of follicle development • Progesterone inhibits LH secretion (neg. feedback loop!) => inhibition of ovulation; also increases mucus viscosity • Both steroids alter endometrium => prevent implantation

  41. Sex Steroids Oral Contraceptives Estrogen Progesterone

  42. Sex Steroids Contraceptives • “Mini Pill”: • Contains only a progesterone (Levonorgestrel, Ethynodiol…) • Used when estrogen in contraindicated (e.g. thrombosis) • Taken daily without interruption • Acts mainly by increasing viscosity of mucus (Mucolytica in cough medicine can cause failure) • Less reliable than combination pill • Postcoital contraceptives (“Morning after pill”) • High dose of progesterone (Levonorgestrel) • Must be taken within 72 hrs • Nausea and vomiting are common side effects • Depot and patch formulations • Injection of oily depot formulations every 3 month • Transdermal delivery systems

  43. Sex Steroids Oral Contraceptives Side effects: • Thrombosis • Hypertension • Intermittant bleeding • Weight gain • Depression • Nausea • Loss of libido Drug interactions: • Steroids are metabolized by P450 enzymes • Minimal dose of steroid is used to prevent risk of thrombosis • Any increase in clearance by P450-inducing drugs can result in contraception failure • Frequent cause of OC failure is diarrhea (diminished time for absorption)

  44. Evolution of Reproduction Among the Vertebrates Vertebrate sexual reproduction evolved in the ocean before vertebrates colonized land Most marine bony fish use external fertilization Male and female gametes are released into the water where fertilization occurs Most other vertebrates use internal fertilization Male gametes are introduced into the female reproductive tract • There are three strategies for internal fertilization • Oviparity • Fertilized eggs are deposited outside mother’s body to complete their development • Ovoviviparity • Fertilized eggs are retained within the mother to complete their development • Young obtain nourishment from egg yolk • Viviparity • Fertilized eggs are retained within the mother to complete their development • Young obtain nourishment from mother’s blood

  45. Three Types of Mammalian Development • Monotremes are oviparous • Lay eggs • Young hatchlings obtain milk by licking mammary glands (they lack nipples) • Marsupials are viviparous • Give birth to incompletely developed fetuses • Complete development in mother’s pouch • Obtain food from nipples in mammary glands • Placentals are viviparous • Retain young in uterus for long periods of development • Fetuses are nourished by the placenta

  46. Mammalian Breeding Patterns • Some mammals are seasonal breeders • Others have reproductive cycles • Periodic release of a mature ovum (ovulation) • Most female mammals have estrous cycles • Females sexually receptive to males only around time of ovulation (estrus) • Apes and humans have menstrual cycles • Females bleed when shedding inner lining of the uterus • Can copulate at any time in their cycle • Cats and rabbits are induced ovulators • Ovulation only after copulation due to LH secretion

  47. 如何決定哺乳動物的性別How Sex is Determined in Mammals • 決定時機：胚胎早期（in embryonic development）即以決定性別 • 胚胎性腺不同；即決定在於Y染色體上的基因：SRY（Sex-determining region of the Y chromosome）。該基因產物可以將性腺轉變為睪丸。

  48. 男性生殖器官Male Reproductive Organs • 睪丸（testis ）產生出睪固酮與精子（sperm） • Enclosed in a hanging sac called the scrotum • 精子發育需要在低溫 • 精子形成（spermatogenesis）在製精細小管（SeminiferousTubules）製造 • 精子將會貯藏於附睪(Epididymis)並成熟之。 • 從附睪至輸精管（vas deferens）至壺腹（ampulla最長最寬的部份，構成輸卵管的三分之二，也是受精處） • At ejaculation they pass into the urethra which empties through the penis • Accessory sex glands: • Empty their secretions into the ducts during ejaculation • Include the seminal vesicles, prostate gland, and bulbourethral glands

  49. 　精子是在雄性生殖器官－睪丸（testes）內製造的，其會經過一系列的加工步驟產生而來，此過程包含了：(1)細胞大小的增加；(2)連續兩次的細胞分裂；(3)使新的細胞由靜止的球體變成細長可動精子的變態情況。　精子是在雄性生殖器官－睪丸（testes）內製造的，其會經過一系列的加工步驟產生而來，此過程包含了：(1)細胞大小的增加；(2)連續兩次的細胞分裂；(3)使新的細胞由靜止的球體變成細長可動精子的變態情況。 • 　　雙套的精原細胞（spermatogonium）會生長轉變成初級精母細胞（perimary spermatocyte），然後初級精母細胞會進行減數分裂之第一次分裂，產生兩個單套的次級精母細胞（secondary spermatocyte），緊接著，每一個次級精母細胞會再進行減數分裂之第二次分裂，產生兩個精細胞（spermatid）。 • 　　之後呢，每一個精細胞會發生蛻變（metamorphosis），即改變它的外形，由較大而球形而且不動的形狀，演變成較小且細長而且又可動的精子（sperm）。典型的精子包含頭、中片和尾等三個部份

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