Male Endocrinology and Reproductive Hormones

Male Endocrinology

Overview

  • Hormones and Cells that Produce Them: Focus on the hormones related to male physiology, their production sites, and functions.

  • Hormone Actions (and Mechanism): Explore how these hormones exert their effects on target cells through specific mechanisms.

  • Hormonal Feedback and Regulation: Discuss the feedback systems that maintain hormone levels.

  • Abuse of Anabolic Steroids: Review the implications of abusing synthetic hormones and their ethical considerations.

Important Readings

  • Senger, pages 214-218.

Male Hypothalamus and Anterior Pituitary

Neurosecretory GnRH Neurons

  • Role: The hypothalamus produces Gonadotropin-Releasing Hormone (GnRH) which is critical for regulatory function in both male and female endocrine systems.

  • Mechanism: GnRH stimulates the anterior pituitary gland to release FSH (Follicle-Stimulating Hormone) and LH (Luteinizing Hormone).

  • Blood Vessels: Hormones secreted from the hypothalamus enter the blood vessels, traveling to endocrine cells in the pituitary gland.

Gonadal Hormones

Overview of Hormones

  • Ovary Steroids:
       - Progesterone (progestin)    - Androstenedione/Testosterone (androgens)    - Estradiol-17b/Estrone (estrogens)

  • Testis Steroids:    - Testosterone (androgen)    - Estradiol-17b (estrogen)

  • Proteins (in Both Testis and Ovary):
       - Inhibin    - Activin    - Oxytocin    - Relaxin

Steroid Hormone Mechanism of Action

  • General Characteristics:   - Steroids (e.g., E2, T) bind to nuclear receptors (act as transcription factors).

Process of Action

  1. Diffusion: Steroids diffuse through the plasma membrane, cytoplasm, and nuclear membrane of the target cell.

  2. Binding: Binding of steroid hormones to nuclear receptors triggers:    - Production of mRNA    - Synthesis of new proteins, including enzymes necessary for reproduction.

Cellular Overview

  • Target Cell Structure:    - Nucleus: Site for mRNA production.    - Cytoplasm: Site for new protein formation.    - Cell Membrane: Interface for hormone-receptor interaction.

Transport of Steroids in Blood

  • Method of Transport:   - Steroids, being lipophilic, bind to large, water-soluble proteins in the bloodstream.

Major Transport Proteins

  1. Sex Steroid Binding Globulin (SSBG)

  2. Albumin

Protein Hormone Mechanism of Action (i.e., LH, FSH)

  1. Receptor Binding: Hormones bind to receptors on the plasma membrane (cannot pass through the membrane).

  2. G-Protein Activation: Binding activates the G protein.

  3. Enzyme Activation:    - Activates Adenylate Cyclase which then produces cAMP.

  4. Protein Kinase A Activation:    - Involves adding phosphate to other kinases, leading to gene transcription.

  5. Cellular Outcomes: Initiates processes required for male sexual function and overall reproductive health.

Sex Steroid Synthesis

Overview

  • Starting Material: Cholesterol, which is converted through various steps to produce different androgens and estrogens.

Steroidogenetic Pathway Chart

  • Key Intermediates:   - Pregnenolone   - Progesterone   - 17 α-OH-Pregnenolone   - 17 α-OH-Progesterone   - Dehydroepiandrosterone (DHEA)   - Androstenedione

  • Final Products:   - Testosterone (from Testis)   - Estradiol (from Ovary)

Enzymatic Conversions

  • Aromatase: Converts androgens to estrogens.

  • 5α-Reductase: Converts testosterone to dihydrotestosterone (DHT).

Male Hormones

Key Hormones

  • FSH (Follicle-stimulating hormone) & LH (Luteinizing hormone): Initially named for their roles in females but operate similarly in males. Previously referred to as Interstitial Cell Stimulating Hormone (ICSH), which was later identified as LH.

  • Testosterone and Androgens:   - Major androgen in mammals, particularly important for male sexual characteristics.

Actions of Testosterone

  • Mechanisms and Functions:   - Converted to Dihydrotestosterone (DHT) by 5α-Reductase.

Effects of Androgens (T and DHT)

  1. Spermatogenesis: Essential for sperm production.

  2. Secondary Sex Characteristics: Include:    - Development of maleness traits (voice deepening, body hair).    - Auricular and pubic hair growth.    - Increased muscle mass and bone density.    - Behavioral traits including increased sex drive.    - Changes in coloration and plumage in certain species.    - Male pattern baldness in older men.

Endocrine Regulation in Males

Two Regulatory Arms

Arm 1:

  • Components:   - Hypothalamus secretes GnRH.   - Anterior Pituitary produces FSH which acts on Sertoli cells to produce Inhibin.   - Feedback: Inhibin exerts negative feedback on ant. pituitary to suppress FSH.

Arm 2:

  • Components:   - Hypothalamus secretes GnRH.   - Anterior Pituitary produces LH affecting Leydig cells which produce testosterone, providing negative feedback on the anterior pituitary.

Temporal Relationships Between GnRH, LH, and FSH in the Male

  • Hormone Concentrations over Time:   - Visual representation of fluctuation patterns in hormone levels over a designated period (hours).

Typical Peripheral Blood Concentrations of LH and Testosterone in Males

  • Graphical Representation:   - Overview of hormonal concentration charts indicating typical levels of LH and Testosterone over time.

Steroid Breakdown

  • Process: Primarily accomplished in the liver, involving enzyme modifications that lead to inactivation.

  • Chemical Modifications: Include the addition of glucuronic acid and sulfate.

Testosterone as a Pro-Hormone

  • Conversion Processes: Testosterone is converted to Estradiol and Dihydrotestosterone (DHT) in target tissues, influencing various developmental processes and secondary sexual characteristics.

Actions Mediated by Testosterone Conversion to Estradiol

  • Functions:   - Differentiation of male external genitalia.   - Development of male internal genital ducts.   - Induction of adult secondary sex characteristics.   - Hypothalamus differentiation.

  • Physiological Impact: Closure of epiphyseal plates in long bones, influencing growth cessation.

  • Efferent Ducts: Importance of estrogen receptors for proper fluid absorption in testicular efferent ducts.

Problems Associated with Low Testosterone

  • Andropause: A gradual decline in testosterone levels with age, ranging from 50-65% from the 20s to 70s.

Associated Symptoms

  • Reduced sexual drive and erectile function.

  • Decreased sperm count and increased breast tissue.

  • Loss of body hair and muscle mass, fat accumulation, and decreased bone density, contributing to osteoporosis.

  • Mood variations and decreased energy levels.

  • Testicular size reduction.

Other Causes of Low Testosterone

  • Factors: Include injury, infection, systemic diseases (such as AIDS), high body fat percentages, Type 2 diabetes, Klinefelter syndrome (XXY), and simply aging.

Testosterone Replacement Therapy (TRT)

  • Controversies: Issues surrounding TRT in older adults.

  • Forms of Administration: Include injections, patches, gels, tablets (some are not legal in the US).

Risks of Testosterone Replacement Therapy

  • Prostate Cancer Risks:   - Importance of careful monitoring, particularly for older males or those with a family history of prostate cancer.

  • Specific Groups at Risk: Men over 40, men with relatives having prostate cancer, men over 50, and African American men are at higher risk.

Anabolic Steroids

  • Definition: Substances that promote anabolic (building) processes in the body, enhancing growth and differentiation of various tissues.

  • Relation to Testosterone: Androgens propagate male characteristics.

  • Legal Uses:   - Commonly utilized in medical treatments, such as for aiding AIDS patients to regain weight, and for addressing anemia.

  • Forms Available: Include pills, creams, patches, tablets, injectables, and sublingual drops.

Anabolic Steroid Abuse

  • Prevalence: Reported use by 1 in 16 high school students (predominantly boys).

  • Testing: Emphasis on testing athletes across collegiate and professional levels for anabolic substance use.

Risks of Anabolic Steroid Abuse

Gender-Specific Effects

Girls:

  • Development of male characteristics such as facial hair, deepening voice, increased body hair, irregularities in menstrual cycles, and clitoral enlargement.

Boys:

  • Manifestations include breast growth, testes shrinkage, and low testosterone production.

Common Effects:

  • Severe acne, baldness, liver abnormalities, mood changes including aggression, paranoia, hallucinations, psychosis, risk of blood clots.

  • Particular Risks in Young Adults: Abusing steroids can halt growth and induce permanent changes in females. Withdrawal often leads to depression and mood swings, with risks tied to impure products and sanitary practices.

Misuse of Steroid Precursors (Prohormones)

  • Definition: Chemical compounds that can be converted by the body into anabolic steroids.

  • Potential for Conversion: Prohormones may also transform into estrogens.

  • Example Compounds:   - Androstenedione   - Androstenediol   - Dehydroepiandrosterone (DHEA)

  • Legality: All but DHEA are illegal in the US. DHEA appears in unregulated nutritional supplements, presenting risks of contamination.

  • IOC Findings: About 1 in 5 supplements are reported to contain anabolic steroids, producing similar side effects as anabolic steroid abuse.

Summary

  • Hormones that regulate female reproduction also play essential roles in male reproductive health, albeit with different regulatory approaches.

  • Androgens are vital for male differentiation and the process of spermatogenesis.

  • The role of testosterone extends beyond being a primary male hormone, serving as a "pro-hormone" through its conversion to DHT and estradiol, both of which fulfill critical physiological roles in males.

  • There is a decline in androgen levels associated with aging. Anabolic steroid abuse is widespread and presents significant health risks.